Affinage

SFTPB

Pulmonary surfactant-associated protein B · UniProt P07988

Length
381 aa
Mass
42.1 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SFTPB encodes surfactant protein B (SP-B), an amphipathic, membrane-active protein essential for the biophysical function of pulmonary surfactant at the alveolar air-liquid interface (PMID:1948032, PMID:8998078). It is synthesized in alveolar type II cells as a ~40-42 kDa glycosylated preproprotein and processed through 25/26-kDa and 18-kDa intermediates to a mature ~7.5-9 kDa peptide, with processing to the active form occurring in a cell-type-specific manner that fails in heterologous cell lines (PMID:2459102, PMID:8460718, PMID:10383422); the NH2-terminal propeptide is necessary and sufficient for trafficking through the secretory pathway and, together with the mature peptide, directs sorting to lamellar bodies (PMID:8703986, PMID:8702672). The mature peptide adopts a ~40-50% alpha-helical, saposin-like fold stabilized by three intrachain disulfides plus an interchain Cys48 bond that creates homodimers (PMID:1390703, PMID:1688355, PMID:1568474, PMID:12135384). At membranes SP-B acts superficially at the lipid/water interface, interacting selectively with anionic phospholipids such as phosphatidylglycerol, ordering head-group regions, mediating divalent-cation-dependent lipid mixing and insertion of lipid from vesicles into monolayers, and reorganizing film micro/nanostructure to confer mechanical stability and reversible film folding at compression (PMID:2397209, PMID:1390835, PMID:1868098, PMID:1932022, PMID:7696261, PMID:11325728, PMID:14695272, PMID:22465066). In vivo SP-B is required dose-dependently for postnatal lung function: its loss causes lethal respiratory distress, phosphatidylglycerol depletion, defective proSP-C processing with accumulation of immature SP-C intermediates, enlarged lamellar bodies, impaired surfactant activity, and pulmonary inflammation (PMID:9092492, PMID:8998078, PMID:7537464, PMID:12639841, PMID:16024721). SP-B expression is regulated transcriptionally and post-transcriptionally by glucocorticoids, IL-6/JAK-STAT signaling, AP-1 family members, and a 3'-UTR element responsive to TPA/TNF-alpha (PMID:8427712, PMID:10409233, PMID:20693312), and extracellular SP-B-containing complexes stimulate further lamellar body exocytosis via P2Y2/ATP/Ca2+ autocrine signaling (PMID:29543530).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1989 High

    Establishing the gene structure and precursor architecture defined SP-B as a single-copy gene encoding a 381-residue precursor processed to a 79-residue mature peptide, framing all subsequent processing studies.

    Evidence cDNA isolation, gene sequencing, Southern blotting and chromosomal mapping

    PMID:2924687

    Open questions at the time
    • Did not define the proteolytic enzymes or sites driving precursor maturation
    • No structural information on the mature peptide
  2. 1990 High

    Biophysical reconstitution showed SP-B selectively orders anionic phospholipid head-group regions, beginning the mechanistic account of how it modifies surfactant membranes.

    Evidence Fluorescence anisotropy with surface- and interior-sensitive probes in DPPC/DPPG bilayers

    PMID:2397209

    Open questions at the time
    • Did not link membrane ordering to surface tension function in vivo
    • Mechanism of PG selectivity not defined at residue level
  3. 1991 High

    Surface-tension, lipid-mixing and monolayer-insertion assays established SP-B's core surface activity and distinguished it functionally from SP-C, identifying charged residues and Trp partitioning as determinants.

    Evidence Synthetic peptide structure-activity, Wilhelmy balance, pyrene lipid-mixing assays, and saposin-repeat homology analysis

    PMID:1390835 PMID:1688355 PMID:1868098 PMID:1932022 PMID:1948032

    Open questions at the time
    • Did not resolve high-resolution structure of the active segment
    • Required divalent cation dependence mechanism unexplained
  4. 1992 High

    Combined structural, spectroscopic and biochemical work defined SP-B's superficial alpha-helical orientation, its disulfide-bonded homodimeric architecture, and its multi-step biosynthetic processing in type II cells.

    Evidence ATR-FTIR, ESR with spin-labeled lipids, disulfide mapping of purified human SP-B, and immunoprecipitation of labeled lung explants

    PMID:1390703 PMID:1550251 PMID:1568474 PMID:2459102 PMID:7696261

    Open questions at the time
    • Trafficking and sorting determinants not yet defined
    • Disulfide topology not connected to function by mutagenesis
  5. 1993 High

    Cell-specific processing and glucocorticoid regulation studies showed mature SP-B is generated only in authentic type II cells and that hormone control acts at both transcription and mRNA stability.

    Evidence Pulse-chase in type II vs CHO cells, nuclear run-on, mRNA stability and cycloheximide assays, plus surface-cycling degradation experiments

    PMID:8216208 PMID:8427712 PMID:8460718

    Open questions at the time
    • Identity of the type II-specific processing proteases unknown
    • Glucocorticoid-responsive cis-elements not mapped
  6. 1996 High

    Domain-deletion analyses resolved which precursor regions control trafficking and lamellar-body targeting, assigning the NH2-terminal propeptide a necessary and sufficient role.

    Evidence Transfection of SP-B deletion constructs into CHO, AtT-20 and PC12 cells with pulse-chase, EndoH assays, immuno-EM and transgenic validation

    PMID:8702672 PMID:8703986

    Open questions at the time
    • Sorting receptor or machinery recognizing the propeptide not identified
    • COOH-propeptide function not yet defined in vivo
  7. 1995 High

    Genetic ablation and human disease samples established that SP-B is dose-dependently essential for lung function and required for correct proteolytic processing of proSP-C.

    Evidence SP-B knockout and heterozygous mice with lung mechanics, plus Western blot of human BAL/amniotic fluid showing aberrant 12-kDa proSP-C intermediate

    PMID:7537464 PMID:8998078

    Open questions at the time
    • Mechanism by which SP-B enables proSP-C processing unresolved
    • Did not separate biophysical from processing contributions to lethality
  8. 1997 High

    In vivo transgenic dissection assigned the C-terminal propeptide a role in proSP-C processing and lamellar-body homeostasis distinct from extracellular surfactant function.

    Evidence SP-B(-/-)/hSP-BΔC transgenic mice with Western blot, lamellar-body EM and lipid biochemistry

    PMID:9092492

    Open questions at the time
    • Molecular basis linking C-propeptide to lamellar-body size unknown
    • Did not identify interacting processing factors
  9. 1999 High

    Cell-type-specific rescue demonstrated that SP-B must be expressed and matured specifically in type II cells, since Clara-cell expression yielded no mature peptide and no rescue.

    Evidence Promoter-targeted transgenic rescue (SP-C vs CCSP promoter) in SP-B(-/-) mice with physiology and Western blot, plus AP-1 promoter regulation mapping

    PMID:10383422 PMID:10409233

    Open questions at the time
    • Cell-type-specific processing machinery still uncharacterized
    • AP-1 regulatory findings from reporter assays in a single lab
  10. 2003 High

    Conditional knockout established a quantitative threshold (~25% of normal) below which SP-B loss causes respiratory failure, integrating lipid, processing and surfactant-activity defects.

    Evidence Doxycycline-regulated conditional SP-B mice with lung mechanics, BAL, phospholipid and in vitro surfactant assays

    PMID:12639841

    Open questions at the time
    • Did not define why PG specifically is depleted on SP-B loss
    • Threshold mechanism not molecularly explained
  11. 2005 High

    Reversible conditional models and peptide mutagenesis linked SP-B deficiency to STAT3-driven pulmonary inflammation and identified Trp9/proline residues governing interfacial reinsertion.

    Evidence Conditional SP-B mice with BAL cytokine ELISA and STAT3 Western blot, plus alanine-scan synthetic peptide surface-pressure assays

    PMID:16024721 PMID:16214863

    Open questions at the time
    • Whether inflammation is direct or secondary to surfactant failure unresolved
    • Residue determinants tested only in N-terminal peptide fragments
  12. 2018 Medium

    Functional studies extended SP-B's role beyond film biophysics to autocrine control of secretion, showing extracellular SP-B complexes drive lamellar-body exocytosis via P2Y2/ATP/Ca2+, while protein-protein interactions modulate its aggregation state.

    Evidence Primary ATII exocytosis assays with P2Y2 pharmacology and Ca2+/ATP measurement, plus FRET/homo-FRET analysis of SP-B aggregation

    PMID:29543530 PMID:29700110

    Open questions at the time
    • P2Y2 signaling shown in primary cells from a single lab without in vivo confirmation
    • Physiological role of SP-B homoaggregation not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The proteases that execute type II cell-specific proSP-B and proSP-C maturation, and the molecular basis by which SP-B enables proSP-C processing and lamellar-body homeostasis, remain unidentified.
  • No processing enzyme identified in the corpus
  • Mechanistic link between SP-B and proSP-C cleavage unresolved
  • No high-resolution structure of full mature SP-B dimer in membrane

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 5 GO:0005198 structural molecule activity 4 GO:0005215 transporter activity 2
Localization
GO:0005576 extracellular region 3 GO:0031410 cytoplasmic vesicle 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9609507 Protein localization 2
Partners
SFTPC
Complex memberships
lamellar bodypulmonary surfactant lipid-protein complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 SP-B enhances the ability of phospholipids to reduce surface tension by increasing lateral stability and molecular order of the phospholipid monolayer; intermittent positively charged residues (Arg) are essential for this activity; tryptophan fluorescence showed SP-B partitions within the phospholipid layer in contact with both polar head groups and acyl side chains. Peptide synthesis, tryptophan fluorescence partitioning assay, Wilhelmy balance surface tension measurements, in vivo instillation studies Science High 1948032
1990 SP-B markedly orders the surface (head-group region) of DPPC/DPPG model membrane bilayers below the gel-to-fluid phase transition temperature, with concentration-dependent effects peaking at 1–2% protein:lipid by weight; SP-B resides primarily in fluid-phase domains and interacts selectively with phosphatidylglycerol. Fluorescence anisotropy with surface-sensitive (6-NBD-PC, 6-NBD-PG) and interior-sensitive (cis-parinaric acid, DPH, trans-parinaric acid) fluorescent probes; fluorescence lifetime measurements Biochemistry High 2397209
1991 SP-B (but not SP-C) mediates lipid mixing between phospholipid vesicles, a process enhanced by negatively charged phospholipids (PG or PI) and divalent cations, and saturated at ~0.2 mol% protein. SP-C was unable to induce lipid mixing under the same conditions. Pyrene-PC fluorescence excimer/monomer ratio lipid-mixing assay with SUVs Biochimica et biophysica acta High 1390835
1991 SP-B present in a preformed phospholipid monolayer promotes lipid insertion from vesicles into the monolayer ~10× more effectively than SP-B present only in vesicles; process requires divalent cations, is dependent on vesicle size, phospholipid concentration, and protein concentration; SP-B binds vesicles directly to the monolayer with ~4× greater capacity than SP-C by weight. Wilhelmy plate monolayer surface pressure measurements; monolayer/vesicle binding assay Biochemistry High 1868098 1932022
1992 SP-B adopts approximately 40–50% alpha-helical conformation both free and when associated with DPPC/PG bilayers; the protein maintains a superficial orientation at the lipid/water interface with electrostatic interactions between charged residues and PG polar headgroups, and small hydrophobic helical segments penetrating slightly into the bilayer; the protein does not alter acyl-chain conformation or orientation. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) of SP-B in lipid bilayers Biochemistry High 1390703
1992 SP-B (but not SP-C) selectively interacts with phosphatidylglycerol over zwitterionic phospholipids in a manner modulated by ionic strength; both SP-B and SP-C reduce the mobility of phospholipid acyl chains in fluid-phase bilayers without affecting gel-phase order on the conventional ESR timescale; SP-B saturates its effect on DPPC bilayers at 20% protein/lipid by weight. Electron spin resonance (ESR) spectroscopy with spin-labeled phospholipids reconstituted with porcine SP-B and SP-C Biochemistry High 7696261
1992 SP-B is synthesized as a 40–42 kDa precursor (Mr) in human alveolar type II epithelial cells and processed through a 25 kDa and 18 kDa intermediate to the mature 7.5–8 kDa peptide (dimer Mr ~18 kDa under nonreducing conditions); SP-B is localized intracellularly in granular inclusions in the apical region of type II-like cells. Immunoprecipitation of [35S]-methionine-labeled fetal lung explants, SDS-PAGE under reducing/nonreducing conditions, immunocytochemistry with anti-SP-B antiserum Journal of applied physiology High 2459102
1989 The human SP-B gene is ~9.5 kb, contains 11 exons and 10 introns, and encodes a 381-amino-acid precursor that is processed to the active 79-residue mature peptide; the gene is present as a single copy and is localized to chromosome 2. cDNA library isolation, gene sequencing, Southern blotting, chromosomal localization DNA High 2924687
1991 The precursor of SP-B (proSP-B) contains three tandem saposin-like (b-type) repeat domains homologous to prosaposin and sulfated glycoprotein 1; the biophysically active mature SP-B corresponds to the second b-type repeat. Sequence database homology search using consensus sequences derived from the SP-B precursor b-type repeats Journal of Biological Chemistry Medium 1688355
1992 Human mature SP-B is 79 residues with a C-terminal methionine and 7 cysteines; three intrachain disulfide bridges link Cys8–Cys77, Cys11–Cys71, and Cys35–Cys46; the remaining Cys48 forms an interchain disulfide creating homodimers. No free thiols are present in native SP-B. Protein purification from human lung, peptide analysis, disulfide bridge mapping by chemical characterization FEBS letters High 1568474
1993 SP-B is degraded during in vitro conversion of large to small surfactant aggregates driven by surface area cycling; small aggregates lack detectable SP-B by immunoblot whereas large aggregates contain SP-B; surface tension-reducing activity is impaired in parallel with SP-B degradation. Surface area cycling in vitro system; differential centrifugation; immunoblot; pulsating-bubble surfactometer Biochemical Journal Medium 8216208
1993 Posttranslational processing of the SP-B precursor to the 9-kDa mature form occurs in a cell-specific manner: isolated type II cells generate the mature 9 kDa form through a series of intermediates, whereas transfected CHO cells produce only the precursor and a 26 kDa intermediate but not the mature 9-kDa peptide. The precursor is glycosylated with N-linked sugars in both cell types. Cell fractionation, [35S]-methionine pulse-chase labeling, SDS-PAGE, immunoprecipitation of SP-B from isolated type II cells and CHO transfectants American Journal of Physiology High 8460718
1996 The NH2-terminal propeptide of SP-B is necessary and sufficient for intracellular trafficking of the mature peptide through the secretory pathway; constructs lacking the NH2-terminal propeptide (SP-BΔN) are retained in the endoplasmic reticulum and rapidly degraded. The first 27 amino acids of SP-B contain a functional signal peptide. Mammalian expression constructs (deletions/truncations of SP-B domains) transfected into CHO cells; [35S]-met/cys labeling, immunoprecipitation, endoglycosidase H sensitivity assay Biochimica et biophysica acta High 8703986
1996 Targeting of SP-B to secretory granules (lamellar bodies) requires both the NH2-terminal propeptide and the mature peptide; the COOH-terminal propeptide is not required for processing or sorting. SP-B processing to the mature form occurs in a cell-specific manner (not in AtT-20 or PC12 cells). Secretion of stored SP-B from AtT-20 cells is stimulated by forskolin/TPA. Transfection of SP-B constructs into AtT-20 and PC12 secretory cell lines; pulse-chase studies; immunoelectron microscopy; in vivo transgenic mouse expression of SP-BΔC Journal of Biological Chemistry High 8702672
1997 The 102-amino acid C-terminal propeptide of SP-B is not required for extracellular surfactant structure or function, but is required for normal SP-C proprotein processing and maintenance of lamellar body size; SP-B(-/-)/hSP-BΔC(+/+) mice showed accumulation of an 11-kDa SP-C processing intermediate, enlarged lamellar bodies, and increased saturated phosphatidylcholine content in lung tissue. Transgenic mouse generation, lung function testing, Western blot analysis, electron microscopy of lamellar bodies, lipid biochemistry Journal of Biological Chemistry High 9092492
1995 SP-B deficiency (homozygous knockout) causes lethal perinatal respiratory distress in mice; heterozygous SP-B(+/-) mice have 50% reduction of alveolar SP-B protein with decreased lung compliance and air trapping, demonstrating a dose-dependent role for SP-B in lung function. Transgenic mouse genetic ablation; lung function testing (inflation/deflation curves, compliance, residual volumes); Western blot and mRNA quantification American Journal of Respiratory Cell and Molecular Biology High 8998078
1995 SP-B deficiency is associated with aberrant processing and secretion of a 12-kDa immature form of SP-C (containing amino-terminal and active peptide epitopes) in bronchoalveolar lavage, which is not detected in healthy adults; this demonstrates that SP-B is required for correct proteolytic processing of proSP-C. Western blot of BAL and amniotic fluid from SP-B-deficient patients with region-specific anti-proSP-C antisera; immunoprecipitation; immunohistochemistry American Journal of Physiology High 7537464
1999 SP-B expression and processing to the mature peptide specifically in alveolar type II cells (not Clara cells) is absolutely required for postnatal lung function; selective restoration of SP-B expression in Clara cells of SP-B(-/-) mice produced no mature SP-B peptide and failed to rescue respiratory function. Cell-type-specific transgenic rescue: SP-C promoter (type II cells) vs. CCSP promoter (Clara cells) driving human SP-B in SP-B(-/-) mice; physiological testing; Western blot for mature SP-B Journal of Biological Chemistry High 10383422
2003 SP-B is required for postnatal lung function in adult mice; withdrawal of doxycycline-regulated SP-B expression caused respiratory failure when alveolar SP-B fell below ~25% of normal, associated with phosphatidylglycerol depletion, accumulation of misprocessed SP-C proprotein in air spaces, increased BAL protein content, and impaired surfactant activity in vitro. Conditional transgenic SP-B knockout mice (doxycycline-regulated); lung mechanics; BAL analysis; phospholipid assay; in vitro surfactant activity measurement American Journal of Physiology. Lung Cellular and Molecular Physiology High 12639841
2005 SP-B deficiency in adult mice is sufficient to cause pulmonary inflammation, including increased alveolar IL-6, IL-1β, MIP-2, and activation of STAT-3 signaling in alveolar macrophages and epithelial cells; restoration of SP-B expression reversed both lung mechanics abnormalities and inflammation. Conditional transgenic SP-B expression with doxycycline withdrawal/restoration; BAL cytokine ELISA; Western blot for STAT-3/p-STAT-3; lung mechanics measurement American Journal of Physiology. Lung Cellular and Molecular Physiology High 16024721
2010 SP-B promotes film formation and sustains mechanical stability of surfactant films at the most compressed states; SP-C alone produces no film stabilization; together they show a slight combined enhancement of film formation. These effects were measured under physiologically relevant conditions. Captive bubble surfactometer with stability test; naturally derived surfactant lipid mixtures with defined protein compositions Biophysical Journal High 21081077
2001 SP-B induces reversible folding transitions at monolayer collapse that allow surfactant components to be retained at the interface during respreading; SP-C and SP-C peptides prevent loss of unsaturated lipids by inducing monolayer-to-multilayer transitions; these are distinct mechanisms. Langmuir isotherms; fluorescence microscopy; atomic force microscopy of model lung surfactant monolayers Biophysical Journal High 11325728
2004 SP-B alters the micro- and nanostructure of DPPC and DPPC/DPPG phospholipid films: it reduces the size and increases the number of condensed microdomains, reduces condensed-like nanodomains in the liquid-expanded phase, increases the LE/LC interface length, and forms segregated 2D clusters at LC/LE domain boundaries; these structural changes provide mechanical resistance to film deformation. Scanning force microscopy (AFM) of Langmuir-Blodgett films transferred to mica; comparison at multiple SP-B concentrations (2–20 wt%) Biophysical Journal High 14695272
2002 The NMR solution structure of SP-B(11-25) in methanol reveals an amphipathic alpha-helix from approximately residue L14 through M21, with a backbone heavy-atom RMSD of 0.09 Å for the helical segment; the distribution of polar residues about the helix axis is structurally significant. Solution NMR (2D NOESY) with simulated annealing structure determination; circular dichroism Biochemistry High 12135384
2005 Within the N-terminal segment of SP-B, tryptophan-9 is critical for optimal affinity of the peptide for the air-water interface and for reinsertion into surface-active films during compression-expansion cycling; prolines at positions 2, 4, and 6 promote a conformation that facilitates rapid insertion into compressed phospholipid monolayers. Synthetic peptide analogs with alanine substitutions; Wilhelmy balance surface pressure measurements; adsorption assays; compression-expansion cycling Biophysical Journal High 16214863
2013 SP-B (and SP-C) induce the formation of channel-like pores (proteolipid channels) in planar lipid membranes; conductance states range from pS to nS, vary with lipid composition and applied potential; ionic selectivity depends on host lipid: anionic selectivity in zwitterionic membranes and cationic selectivity in negatively charged lipid membranes, demonstrating lipid functional involvement. Electrophysiology (planar bilayer recordings) with SP-B, SP-C, or native mixtures reconstituted in planar lipid membranes of varying composition Biophysical Journal High 23332067
2011 SP-B and SP-C increase membrane permeability to the fluorescent probe FM 1-43 and to calcein; vesicles containing only SP-B are stable but prone to vesicle-vesicle interactions, whereas vesicles with only SP-C are extremely dynamic and prone to rupture; their combined action provides unique modulation of membrane structure and dynamics confirmed by electron microscopy. Fluorescence probe incorporation assays (FM 1-43, Nile Red, calcein); electron microscopy of vesicle structures; giant oligolamellar vesicle imaging Biochemical Journal Medium 21679160
2018 SP-B promotes exocytosis of lamellar bodies by alveolar type II cells; extracellular lipid-protein complexes containing SP-B activate the P2Y2 purinergic signaling pathway via ATP release, triggering Ca2+-dependent surfactant secretion through an autocrine/paracrine mechanism. Primary ATII cell culture; exocytosis assays; P2Y2 receptor pharmacological inhibition; ATP release measurement; Ca2+ signaling assays FASEB Journal Medium 29543530
1993 Glucocorticoids regulate SP-B expression primarily by increasing both the transcription rate (~2.8-fold by nuclear run-on) and SP-B mRNA stability (t1/2 increased from 7.5 to 18.8 h); cycloheximide does not block glucocorticoid induction of SP-B mRNA (distinguishing it from SP-C, which requires ongoing protein synthesis), demonstrating a direct primary glucocorticoid response at the SP-B gene. Nuclear run-on transcription assays; actinomycin D mRNA stability assays; [3H]uridine label-chase; cycloheximide experiments in human fetal lung explants American Journal of Respiratory Cell and Molecular Biology High 8427712
1994 TPA and TNF-alpha inhibit SP-B expression by decreasing SP-B mRNA stability (not by decreasing transcription rate); this inhibitory effect is mediated by a cis-acting element in the 3'-UTR of SP-B mRNA; dexamethasone decreases these inhibitory effects. Stable transfection of H441-4 cells with chimeric TK-hGH constructs containing SP-B 3'-UTR; mRNA decay assays; TPA and TNF-alpha treatment American Journal of Physiology Medium 8048538
1999 AP-1 family members differentially regulate SP-B promoter activity via distinct cis-acting elements: JunD enhances SP-B promoter activity through a proximal AP-1 site (-18 to -10 bp) overlapping a TTF-1 site, while c-Jun and JunB inhibit through both this proximal site and a distal composite site (-370 to -364 bp); c-Fos has no effect. Luciferase reporter assays in MLE-15 cells; promoter deletion mutants; site-directed mutagenesis of AP-1 binding sites; recombinant AP-1 family member overexpression American Journal of Physiology Medium 10409233
2010 Glucocorticoids potentiate IL-6-induced SP-B mRNA expression through the JAK-STAT signaling pathway; glucocorticoids increase the expression of the IL-6 receptor α-subunit (IL-6Rα) at the mRNA and protein level, thereby enhancing IL-6-induced STAT3 phosphorylation and SP-B transcription; this synergism is blocked by a JAK inhibitor. H441 cell culture; RT-PCR; Western blot for STAT3 and phospho-STAT3; JAK inhibitor pharmacology; IL-6Rα expression analysis; glucocorticoid receptor assay American Journal of Physiology. Lung Cellular and Molecular Physiology Medium 20693312
2006 Oxidation of SP-B by reactive oxygen species (hypochlorous acid or Fenton reaction) causes structural alterations (altered Coomassie/silver staining, decreased antibody reactivity) that produce greater loss of surfactant biophysical activity than lipid oxidation alone; addition of unoxidized SP-B can partially rescue samples containing oxidized SP-C, but not vice versa. Reconstitution experiments with oxidized vs. control SP-B and SP-C isolated from bovine lipid extract surfactant; pulsating bubble surfactometer; Western blot; protein carbonyl assay; Coomassie and silver staining Biophysical Journal Medium 16443649
1992 SP-B-based surfactant preparations are markedly less susceptible to inhibition by fibrinogen than SP-C-based or protein-free preparations; addition of small amounts of SP-B to SP-C-based preparations dose-dependently reduces their fibrinogen sensitivity; anti-SP-B monoclonal antibody treatment increases fibrinogen sensitivity of calf lung surfactant extract. Pulsating-bubble surfactometer with fibrinogen inhibition; anti-SP-B monoclonal antibody blocking experiment; comparison of SP-B, recombinant SP-C and combined surfactants American Journal of Physiology Medium 1550251
2009 SP-B dramatically alters vesicle collapse dynamics on silica surfaces: it reduces intact vesicle accumulation before collapse and enables stepwise buildup of multilayered lipid deposits; multilayer accumulation requires SP-B in both receptor and arriving membranes and a comparable phospholipid charge context. Quartz crystal microbalance with dissipation (QCM-D) monitoring supported bilayer formation from phospholipid vesicles Biophysical Journal Medium 19651035
2018 SP-B forms homoaggregates at low lipid:protein ratios (1:1000) as detected by static self-quenching and homo-FRET of BODIPY-FL labeled SP-B; SP-C modulates SP-B aggregation state in a concentration-dependent manner through direct protein-protein interactions, with under-stoichiometric SP-C increasing SP-B emission (disrupting SP-B aggregates) and over-stoichiometric SP-C quenching Marina Blue SP-C fluorescence; these interactions are compartmentalized in full surfactant membranes but not in pure POPC vesicles. Steady-state and time-resolved fluorescence spectroscopy (FRET, homo-FRET, fluorescence quenching) with BODIPY-FL SP-B and Marina Blue SP-C in reconstituted vesicles Journal of Biological Chemistry Medium 29700110
2012 SP-B topology in phospholipid membranes is superficial (peripheral) rather than deeply penetrating: FRET analysis from single Trp in SP-B to fluorescently labeled phospholipids is consistent with superficial orientation models, discarding deep bilayer penetration; SP-B shows selectivity for anionic over zwitterionic phospholipids in POPC membranes but no selectivity in full surfactant lipid membranes (suggesting saturation of anionic lipid binding sites by endogenous PG). Time-resolved fluorescence/FRET spectroscopy (donor Trp in SP-B, acceptor fluorescent phospholipids) in POPC and full surfactant lipid extract bilayers Biochimica et biophysica acta Medium 22465066
2015 Ozone exposure (∼2 ppm) causes rapid oxidation of SP-B peptides at the air-water interface, evidenced by increased surface tension and loss of Trp fluorescence; oxidized SP-B does not solubilize but remains at the interface with altered hydration; no peptide cleavage occurs but oligomerization increases and partial unfolding is detected; lipids do not protect SP-B from oxidation. Neutron and X-ray reflectivity; surface tension measurement; fluorescence spectroscopy; product analysis Biochemistry Medium 26270023

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Pulmonary surfactant protein B (SP-B): structure-function relationships. Science (New York, N.Y.) 279 1948032
1991 Characterization of lipid insertion into monomolecular layers mediated by lung surfactant proteins SP-B and SP-C. Biochemistry 179 1932022
2000 Allelic heterogeneity in hereditary surfactant protein B (SP-B) deficiency. American journal of respiratory and critical care medicine 178 10712351
2004 Alterations in SP-B and SP-C expression in neonatal lung disease. Annual review of physiology 160 14977415
2000 Polymorphisms of human SP-A, SP-B, and SP-D genes: association of SP-B Thr131Ile with ARDS. Clinical genetics 154 11076040
1995 Aberrant processing of surfactant protein C in hereditary SP-B deficiency. The American journal of physiology 151 7537464
1990 Surfactant protein SP-B induces ordering at the surface of model membrane bilayers. Biochemistry 149 2397209
2003 SP-B deficiency causes respiratory failure in adult mice. American journal of physiology. Lung cellular and molecular physiology 143 12639841
2015 Activation of the GLP-1 Receptor by Liraglutide Increases ACE2 Expression, Reversing Right Ventricle Hypertrophy, and Improving the Production of SP-A and SP-B in the Lungs of Type 1 Diabetes Rats. Endocrinology 141 26196539
1991 Interaction of lipid vesicles with monomolecular layers containing lung surfactant proteins SP-B or SP-C. Biochemistry 139 1868098
1992 Secondary structure and orientation of the surfactant protein SP-B in a lipid environment. A Fourier transform infrared spectroscopy study. Biochemistry 134 1390703
1989 Structure and organization of the gene encoding human pulmonary surfactant proteolipid SP-B. DNA (Mary Ann Liebert, Inc.) 134 2924687
2001 Effects of lung surfactant proteins, SP-B and SP-C, and palmitic acid on monolayer stability. Biophysical journal 130 11325728
1995 Interactions of hydrophobic lung surfactant proteins SP-B and SP-C with dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol bilayers studied by electron spin resonance spectroscopy. Biochemistry 127 7696261
1997 Decreased lung compliance and air trapping in heterozygous SP-B-deficient mice. American journal of respiratory cell and molecular biology 123 8998078
1994 Temporal-spatial distribution of SP-B and SP-C proteins and mRNAs in developing respiratory epithelium of human lung. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 121 8064126
2010 Combined and independent action of proteins SP-B and SP-C in the surface behavior and mechanical stability of pulmonary surfactant films. Biophysical journal 104 21081077
1993 Degradation of surfactant-associated protein B (SP-B) during in vitro conversion of large to small surfactant aggregates. The Biochemical journal 103 8216208
1997 Pulmonary dysfunction in neonatal SP-B-deficient mice. The American journal of physiology 96 9357864
2002 Serum levels of CC16, SP-A and SP-B reflect tobacco-smoke exposure in asymptomatic subjects. The European respiratory journal 93 12449168
1998 Association of pulmonary surfactant protein A (SP-A) gene and respiratory distress syndrome: interaction with SP-B. Pediatric research 92 9475280
1991 Effects of maternal dexamethasone on expression of SP-A, SP-B, and SP-C in the fetal rat lung. American journal of respiratory cell and molecular biology 86 2015097
1995 Keratinocyte growth factor increases mRNAs for SP-A and SP-B in adult rat alveolar type II cells in culture. The American journal of physiology 84 7573468
2006 Reactive oxygen species inactivation of surfactant involves structural and functional alterations to surfactant proteins SP-B and SP-C. Biophysical journal 82 16443649
2001 Intra-amniotic endotoxin increases pulmonary surfactant proteins and induces SP-B processing in fetal sheep. American journal of physiology. Lung cellular and molecular physiology 81 11159007
1997 Combinations of fluorescently labeled pulmonary surfactant proteins SP-B and SP-C in phospholipid films. Biophysical journal 81 9168039
2005 Reversibility of lung inflammation caused by SP-B deficiency. American journal of physiology. Lung cellular and molecular physiology 78 16024721
1993 Lung surfactant proteins, SP-B and SP-C, alter the thermodynamic properties of phospholipid membranes: a differential calorimetry study. Biochemistry 77 8422370
1993 Differential glucocorticoid regulation of the pulmonary hydrophobic surfactant proteins SP-B and SP-C. American journal of respiratory cell and molecular biology 75 8427712
1992 Lipid mixing is mediated by the hydrophobic surfactant protein SP-B but not by SP-C. Biochimica et biophysica acta 75 1390835
1992 Localization of surfactant-associated proteins SP-A and SP-B mRNA in rabbit fetal lung tissue by in situ hybridization. American journal of respiratory cell and molecular biology 75 1520494
2004 Effect of pulmonary surfactant protein SP-B on the micro- and nanostructure of phospholipid films. Biophysical journal 74 14695272
2012 Structure-function correlations of pulmonary surfactant protein SP-B and the saposin-like family of proteins. European biophysics journal : EBJ 73 22996193
1998 An SP-B gene mutation responsible for SP-B deficiency in fatal congenital alveolar proteinosis: evidence for a mutation hotspot in exon 4. Molecular genetics and metabolism 71 9682215
1994 Dynamic surface properties of pulmonary surfactant proteins SP-B and SP-C and their mixtures with dipalmitoylphosphatidylcholine. Biochemistry 70 7993894
2018 Surfactant protein B (SP-B) enhances the cellular siRNA delivery of proteolipid coated nanogels for inhalation therapy. Acta biomaterialia 68 30118853
2012 New surfactant with SP-B and C analogs gives survival benefit after inactivation in preterm lambs. PloS one 68 23091635
1996 Structural requirements for intracellular transport of pulmonary surfactant protein B (SP-B). Biochimica et biophysica acta 68 8703986
1996 Structural requirements for targeting of surfactant protein B (SP-B) to secretory granules in vitro and in vivo. The Journal of biological chemistry 66 8702672
1992 Differential sensitivity to fibrinogen inhibition of SP-C- vs. SP-B-based surfactants. The American journal of physiology 66 1550251
1996 Transcriptional regulation of human pulmonary surfactant proteins SP-B and SP-C by glucocorticoids. American journal of respiratory cell and molecular biology 63 8652188
2001 Surfactant protein (SP) B associations and interactions with SP-A in white and black subjects with respiratory distress syndrome. Pediatrics international : official journal of the Japan Pediatric Society 62 11737731
2000 Microstructure and dynamic surface properties of surfactant protein SP-B/dipalmitoylphosphatidylcholine interfacial films spread from lipid-protein bilayers. European biophysics journal : EBJ 62 10968212
1997 Rescue of SP-B knockout mice with a truncated SP-B proprotein. Function of the C-terminal propeptide. The Journal of biological chemistry 61 9092492
1993 Pulmonary surfactant-associated protein SP-B has little effect on acyl chains in dipalmitoylphosphatidylcholine dispersions. Biochemistry 61 8476867
1991 Homology of the precursor of pulmonary surfactant-associated protein SP-B with prosaposin and sulfated glycoprotein 1. The Journal of biological chemistry 61 1688355
1990 Phorbol ester inhibits surfactant protein SP-A and SP-B expression. The Journal of biological chemistry 57 2249989
1991 Effects of surfactant-associated protein SP-B synthetic analogs on the structure and surface activity of model membrane bilayers. Chemistry and physics of lipids 56 1814640
1995 ELISA technique for quantification of surfactant protein B (SP-B) in bronchoalveolar lavage fluid. American journal of respiratory and critical care medicine 55 7582290
1994 SP-A, SP-B, and SP-C in surfactant subtypes around birth: reexamination of alveolar life cycle of surfactant. The American journal of physiology 54 8179020
1992 Effect of pulmonary surfactant protein B (SP-B) and calcium on phospholipid adsorption and squeeze-out of phosphatidylglycerol from binary phospholipid monolayers containing dipalmitoylphosphatidylcholine. Biochimica et biophysica acta 53 1606172
1999 Surfactant protein B (SP-B) -/- mice are rescued by restoration of SP-B expression in alveolar type II cells but not Clara cells. The Journal of biological chemistry 52 10383422
1991 Appearance of surfactant proteins, SP-A and SP-B, in developing rat lung and the effects of in vivo dexamethasone treatment. Biochimica et biophysica acta 51 1991156
2013 Hydrophobic pulmonary surfactant proteins SP-B and SP-C induce pore formation in planar lipid membranes: evidence for proteolipid pores. Biophysical journal 49 23332067
2012 SP-B and SP-C containing new synthetic surfactant for treatment of extremely immature lamb lung. PloS one 49 22808033
2010 Synthetic surfactant based on analogues of SP-B and SP-C is superior to single-peptide surfactants in ventilated premature rabbits. Neonatology 49 20110733
1995 Conformational flexibility of pulmonary surfactant proteins SP-B and SP-C, studied in aqueous organic solvents. Biochimica et biophysica acta 49 7893740
1999 SP-B refining of pulmonary surfactant phospholipid films. The American journal of physiology 48 10600889
1996 Overexpression of surfactant protein SP-A, SP-B, and SP-C mRNA in rat lungs with lipopolysaccharide-induced injury. Laboratory investigation; a journal of technical methods and pathology 48 8569184
1988 Identification of surfactant proteolipid SP-B in human surfactant and fetal lung. Journal of applied physiology (Bethesda, Md. : 1985) 47 2459102
2011 A combined action of pulmonary surfactant proteins SP-B and SP-C modulates permeability and dynamics of phospholipid membranes. The Biochemical journal 45 21679160
2018 Synthetic surfactants with SP-B and SP-C analogues to enable worldwide treatment of neonatal respiratory distress syndrome and other lung diseases. Journal of internal medicine 44 30357986
1997 Different modes of interaction of pulmonary surfactant protein SP-B in phosphatidylcholine bilayers. The Biochemical journal 44 9355744
2018 Genetic Association of Pulmonary Surfactant Protein Genes, SFTPA1, SFTPA2, SFTPB, SFTPC, and SFTPD With Cystic Fibrosis. Frontiers in immunology 42 30333828
1996 Roles of SP-A, SP-B, and SP-C in modulation of lipid uptake by pulmonary epithelial cells in vitro. The American journal of physiology 42 8772529
2005 Critical structure-function determinants within the N-terminal region of pulmonary surfactant protein SP-B. Biophysical journal 41 16214863
1991 Hormonal effects on the surfactant protein B (SP-B) mRNA in cultured fetal rat lung. American journal of respiratory cell and molecular biology 39 1850607
2005 Partial SP-B deficiency perturbs lung function and causes air space abnormalities. American journal of physiology. Lung cellular and molecular physiology 38 15722377
2002 Kinetics of phospholipid insertion into monolayers containing the lung surfactant proteins SP-B or SP-C. European biophysics journal : EBJ 38 12046897
1996 Racial differences in allelic distribution at the human pulmonary surfactant protein B gene locus (SP-B). Experimental lung research 37 8872090
2003 Analysis of 40 sporadic or familial neonatal and pediatric cases with severe unexplained respiratory distress: relationship to SFTPB. American journal of medical genetics. Part A 36 12784301
1999 Compound SFTPB 1549C-->GAA (121ins2) and 457delC heterozygosity in severe congenital lung disease and surfactant protein B (SP-B) deficiency. Human mutation 36 10571948
1995 Mapping the human pulmonary surfactant-associated protein B gene (SFTP3) to chromosome 2p12-->p11.2. Cytogenetics and cell genetics 36 7956367
1993 Full length synthetic surfactant proteins, SP-B and SP-C, reduce surfactant inactivation by serum. Biochimica et biophysica acta 35 8323972
2010 Palmitoylation of pulmonary surfactant protein SP-C is critical for its functional cooperation with SP-B to sustain compression/expansion dynamics in cholesterol-containing surfactant films. Biophysical journal 34 21081071
2002 Deficiency of SP-B reveals protective role of SP-C during oxygen lung injury. Journal of applied physiology (Bethesda, Md. : 1985) 34 11796659
1989 Isolation and characterization of the cDNA for pulmonary surfactant-associated protein-B (SP-B) in the rabbit. Biochemical and biophysical research communications 34 2469419
2002 NMR structure of lung surfactant peptide SP-B(11-25). Biochemistry 33 12135384
2001 Lipid-protein interactions of hydrophobic proteins SP-B and SP-C in lung surfactant assembly and dynamics. Pediatric pathology & molecular medicine 33 11699574
1997 Pulmonary surfactant protein SP-B interacts similarly with dipalmitoylphosphatidylglycerol and dipalmitoylphosphatidylcholine in phosphatidylcholine/phosphatidylglycerol mixtures. Biochemistry 33 9100011
1993 Cell-specific posttranslational processing of the surfactant-associated protein SP-B. The American journal of physiology 33 8460718
2018 Pulmonary surfactant protein SP-B promotes exocytosis of lamellar bodies in alveolar type II cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32 29543530
1993 Surfactant-associated proteins (SP-A, SP-B) are increased proportionally to alveolar phospholipids in sheep silicosis. Lung 32 8426464
2003 Effect of hydrophobic surfactant proteins SP-B and SP-C on binary phospholipid monolayers: II. Infrared external reflectance-absorption spectroscopy. Biophysical journal 31 12524286
1994 3'-untranslated region of SP-B mRNA mediates inhibitory effects of TPA and TNF-alpha on SP-B expression. The American journal of physiology 31 8048538
1992 Human surfactant polypeptide SP-B. Disulfide bridges, C-terminal end, and peptide analysis of the airway form. FEBS letters 31 1568474
2010 Glucocorticoids potentiate IL-6-induced SP-B expression in H441 cells by enhancing the JAK-STAT signaling pathway. American journal of physiology. Lung cellular and molecular physiology 29 20693312
2012 Topology and lipid selectivity of pulmonary surfactant protein SP-B in membranes: Answers from fluorescence. Biochimica et biophysica acta 28 22465066
2018 Homo- and hetero-oligomerization of hydrophobic pulmonary surfactant proteins SP-B and SP-C in surfactant phospholipid membranes. The Journal of biological chemistry 27 29700110
1999 Regulation of mouse SP-B gene promoter by AP-1 family members. The American journal of physiology 27 10409233
1998 Rotational dynamics of spin-labelled surfactant-associated proteins SP-B and SP-C in dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol bilayers. Biochimica et biophysica acta 27 9858708
2009 Surfactant protein SP-B strongly modifies surface collapse of phospholipid vesicles: insights from a quartz crystal microbalance with dissipation. Biophysical journal 26 19651035
2002 Dimeric surfactant protein B peptide sp-b(1-25) in neonatal and acute respiratory distress syndrome. Experimental lung research 26 12490037
1994 Differential expressions of surfactant protein SP-A, SP-B, and SP-C mRNAs in rats with streptozotocin-induced diabetes demonstrated by in situ hybridization. American journal of respiratory cell and molecular biology 26 7917308
2014 Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury. PeerJ 25 24883253
2000 Aberrant SP-B mRNA in lung tissue of patients with congenital alveolar proteinosis (CAP). Clinical genetics 25 10852370
2023 Surfactant Proteins SP-B and SP-C in Pulmonary Surfactant Monolayers: Physical Properties Controlled by Specific Protein-Lipid Interactions. Langmuir : the ACS journal of surfaces and colloids 24 36917773
2015 Environmental Pollutant Ozone Causes Damage to Lung Surfactant Protein B (SP-B). Biochemistry 24 26270023
2008 Surfactant proteins SP-B and SP-C and their precursors in bronchoalveolar lavages from children with acute and chronic inflammatory airway disease. BMC pulmonary medicine 24 18405368
2012 Synergistic effect of caffeine and glucocorticoids on expression of surfactant protein B (SP-B) mRNA. PloS one 23 23272120

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