pulmonary surfactant associated protein b


Summary: A pulmonary surfactant associated-protein that plays an essential role in alveolar stability by lowering the surface tension at the air-liquid interface. Inherited deficiency of pulmonary surfactant-associated protein B is one cause of RESPIRATORY DISTRESS SYNDROME, NEWBORN.

Top Publications

  1. Freites J, Choi Y, Tobias D. Molecular dynamics simulations of a pulmonary surfactant protein B peptide in a lipid monolayer. Biophys J. 2003;84:2169-80 pubmed
  2. Ueno T, Linder S, Na C, Rice W, Johansson J, Weaver T. Processing of pulmonary surfactant protein B by napsin and cathepsin H. J Biol Chem. 2004;279:16178-84 pubmed
    ..These results suggest that napsin, cathepsin H, and at least one other enzyme are involved in maturation of the biologically active SP-B peptide. ..
  3. Hamvas A, Wegner D, Trusgnich M, Madden K, Heins H, Liu Y, et al. Genetic variant characterization in intron 4 of the surfactant protein B gene. Hum Mutat. 2005;26:494-5 pubmed
    ..7, 95% CI 1.0-7.2). Reliable characterization of genetic variants in intron 4 requires both a high fidelity polymerase and sequencing of variant alleles. ..
  4. Booth V, Waring A, Walther F, Keough K. NMR structures of the C-terminal segment of surfactant protein B in detergent micelles and hexafluoro-2-propanol. Biochemistry. 2004;43:15187-94 pubmed
  5. Makri V, Hospes B, Stoll Becker S, Borkhardt A, Gortner L. Polymorphisms of surfactant protein B encoding gene: modifiers of the course of neonatal respiratory distress syndrome?. Eur J Pediatr. 2002;161:604-8 pubmed
    ..we suggest that polymorphisms in intron 4 of the surfactant protein B gene independently modify the course of neonatal respiratory distress syndrome. ..
  6. Brasch F, Johnen G, Winn Brasch A, Guttentag S, Schmiedl A, Kapp N, et al. Surfactant protein B in type II pneumocytes and intra-alveolar surfactant forms of human lungs. Am J Respir Cell Mol Biol. 2004;30:449-58 pubmed
    ..In human lungs, mature SP-B is involved in the structural organization of lamellar bodies and tubular myelin by the formation of core particles. ..
  7. Tredano M, Griese M, de Blic J, Lorant T, Houdayer C, Schumacher S, et al. Analysis of 40 sporadic or familial neonatal and pediatric cases with severe unexplained respiratory distress: relationship to SFTPB. Am J Med Genet A. 2003;119A:324-39 pubmed
    ..When disease loci are identified, patient genotyping will be crucial as a diagnostic aid, for devising proper treatment, and as a basis for genetic counseling. ..
  8. Nogee L. Genetic mechanisms of surfactant deficiency. Biol Neonate. 2004;85:314-8 pubmed
    ..The clinical and laboratory features associated with these genetic disorders, along with their implications for the understanding of normal surfactant metabolism, are reviewed...
  9. Nogee L. Alterations in SP-B and SP-C expression in neonatal lung disease. Annu Rev Physiol. 2004;66:601-23 pubmed

More Information


  1. Seurynck Servoss S, Dohm M, Barron A. Effects of including an N-terminal insertion region and arginine-mimetic side chains in helical peptoid analogues of lung surfactant protein B. Biochemistry. 2006;45:11809-18 pubmed
  2. Brasch F, Ochs M, Kahne T, Guttentag S, Schauer Vukasinovic V, Derrick M, et al. Involvement of napsin A in the C- and N-terminal processing of surfactant protein B in type-II pneumocytes of the human lung. J Biol Chem. 2003;278:49006-14 pubmed
    ..Two of the four processing products generated in vitro were also detected in type-II pneumocytes. In conclusion, our results show that napsin A is involved in the N- and C-terminal processing of proSP-B in type-II pneumocytes. ..
  3. Seifart C, Plagens A, Brödje D, Müller B, von Wichert P, Floros J. Surfactant protein B intron 4 variation in German patients with COPD and acute respiratory failure. Dis Markers. 2002;18:129-36 pubmed
    ..5%, p = 0.003, OR 4.9, 95% CI: 1.76-13.6). The data indicate that SP-B intron 4 variants may associate with increased risk of ARF in COPD and may be used as a marker of susceptibility in this disease subgroup. ..
  4. Sarker M, Waring A, Walther F, Keough K, Booth V. Structure of mini-B, a functional fragment of surfactant protein B, in detergent micelles. Biochemistry. 2007;46:11047-56 pubmed
    ..Interhelix interactions are stabilized by both disulfide bonds and by interleaving of hydrophobic side chains from the two helices...
  5. Li J, Ikegami M, Na C, Hamvas A, Espinassous Q, Chaby R, et al. N-terminally extended surfactant protein (SP) C isolated from SP-B-deficient children has reduced surface activity and inhibited lipopolysaccharide binding. Biochemistry. 2004;43:3891-8 pubmed
    ..The results of this study indicate that the early postnatal fatal respiratory distress seen in SP-B-deficient children is combined with the near absence of active variants of SP-C. ..
  6. Walther F, Hernandez Juviel J, Gordon L, Sherman M, Waring A. Dimeric surfactant protein B peptide sp-b(1-25) in neonatal and acute respiratory distress syndrome. Exp Lung Res. 2002;28:623-40 pubmed
    ..The data suggest that dSP-B(1-25) is more efficient in restoring lung function in neonatal RDS and ARDS than mSP-B(1-25) surfactant. ..
  7. Merrill J, Ballard R, Cnaan A, Hibbs A, Godinez R, Godinez M, et al. Dysfunction of pulmonary surfactant in chronically ventilated premature infants. Pediatr Res. 2004;56:918-26 pubmed
    ..We conclude that most premature infants requiring continued respiratory support after 7 d of age experience transient episodes of dysfunctional surfactant that are associated with a deficiency of SP-B and SP-C. ..
  8. Marttila R, Haataja R, Guttentag S, Hallman M. Surfactant protein A and B genetic variants in respiratory distress syndrome in singletons and twins. Am J Respir Crit Care Med. 2003;168:1216-22 pubmed
    ..Genetic and environmental variation may influence intracellular processing of surfactant complex and the susceptibility to RDS. ..
  9. Hawgood S. Surfactant protein B: structure and function. Biol Neonate. 2004;85:285-9 pubmed
    ..This review will focus on just one of the apoproteins, surfactant protein B, with a description of protein structure and the actions of surfactant protein B on surfactant lipid membranes. ..
  10. Serrano A, Perez Gil J. Protein-lipid interactions and surface activity in the pulmonary surfactant system. Chem Phys Lipids. 2006;141:105-18 pubmed
    ..The understanding of the mechanisms of action of these proteins is critical to approach the design and development of new clinical surfactant preparations for therapeutical applications. ..
  11. Hamvas A, Wegner D, Carlson C, Bergmann K, Trusgnich M, Fulton L, et al. Comprehensive genetic variant discovery in the surfactant protein B gene. Pediatr Res. 2007;62:170-5 pubmed
  12. Walther F, Hernandez Juviel J, Mercado P, Gordon L, Waring A. Surfactant with SP-B and SP-C analogues improves lung function in surfactant-deficient rats. Biol Neonate. 2002;82:181-7 pubmed
  13. Lee H, Kandasamy S, Larson R. Molecular dynamics simulations of the anchoring and tilting of the lung-surfactant peptide SP-B1-25 in palmitic acid monolayers. Biophys J. 2005;89:3807-21 pubmed
    ..Our work indicates that the factors controlling orientation of small peptides in lipid layers can now be uncovered through molecular dynamics simulations. ..
  14. Whitsett J, Weaver T. Hydrophobic surfactant proteins in lung function and disease. N Engl J Med. 2002;347:2141-8 pubmed
  15. Guttentag S, Robinson L, Zhang P, Brasch F, Buhling F, Beers M. Cysteine protease activity is required for surfactant protein B processing and lamellar body genesis. Am J Respir Cell Mol Biol. 2003;28:69-79 pubmed
    ..Our data show that a cysteine protease is involved in SP-B processing, lamellar body genesis, and SP-C processing, and suggest that Cathepsin H is the most likely candidate protease. ..
  16. Seurynck S, Patch J, Barron A. Simple, helical peptoid analogs of lung surfactant protein B. Chem Biol. 2005;12:77-88 pubmed
    ..The extent of biomimicry appears to correlate with peptoid helicity and lipophilicity. These biostable oligomers could serve in a synthetic surfactant replacement to treat respiratory distress syndrome. ..
  17. Yang M, Guo Y, Liu C, Weissler J, Yang Y. The TTF-1/TAP26 complex differentially modulates surfactant protein-B (SP-B) and -C (SP-C) promoters in lung cells. Biochem Biophys Res Commun. 2006;344:484-90 pubmed
    ..Thus, a dimerized complex structure was needed for advanced promoter activity. This result also provided a molecular mechanism by which both the SP-B and SP-C promoters could be differentially regulated by the same complex. ..
  18. Wang G, Christensen N, Wigdahl B, Guttentag S, Floros J. Differences in N-linked glycosylation between human surfactant protein-B variants of the C or T allele at the single-nucleotide polymorphism at position 1580: implications for disease. Biochem J. 2003;369:179-84 pubmed
    ..Further, we speculate that, given the fact that this SNP is found frequently in the general population, N-linked glycosylation at residue Asn129 interferes with SP-B processing, secretion and folding under certain disease conditions. ..
  19. Ryan M, Qi X, Serrano A, Ikegami M, Perez Gil J, Johansson J, et al. Mapping and analysis of the lytic and fusogenic domains of surfactant protein B. Biochemistry. 2005;44:861-72 pubmed
  20. Li C, Zhu N, Tan R, Ballard P, Derynck R, Minoo P. Transforming growth factor-beta inhibits pulmonary surfactant protein B gene transcription through SMAD3 interactions with NKX2.1 and HNF-3 transcription factors. J Biol Chem. 2002;277:38399-408 pubmed
    ..1 was not affected. We conclude that SMAD3 interactions with the positive regulators NKX2.1 and HNF-3 underlie the molecular basis for TGF-beta-induced repression of Sp-B gene transcription. ..
  21. Ryan M, Akinbi H, Serrano A, Perez Gil J, Wu H, McCormack F, et al. Antimicrobial activity of native and synthetic surfactant protein B peptides. J Immunol. 2006;176:416-25 pubmed
    ..These results suggest that the role of endogenous SP-B in host defense may be limited; however, synthetic peptides derived from SP-B may be useful in the treatment of bacterial pneumonias. ..
  22. Walther F, Hernandez Juviel J, Gordon L, Waring A, Stenger P, Zasadzinski J. Comparison of three lipid formulations for synthetic surfactant with a surfactant protein B analog. Exp Lung Res. 2005;31:563-79 pubmed
    ..Lipid composition plays a crucial role in the in vitro and in vivo functions of SP-B(1-25) in surfactant preparations. ..
  23. Chang Y, Wang Z, Schwan A, Wang Z, Holm B, Baatz J, et al. Surface properties of sulfur- and ether-linked phosphonolipids with and without purified hydrophobic lung surfactant proteins. Chem Phys Lipids. 2005;137:77-93 pubmed
    ..The high activity and inhibition resistance of synthetic surfactants containing DEPN-8 or SO(2)-lipid plus SP-B/SP-C are promising for future applications in treating surfactant dysfunction in inflammatory lung injury. ..
  24. Walther F, Waring A, Sherman M, Zasadzinski J, Gordon L. Hydrophobic surfactant proteins and their analogues. Neonatology. 2007;91:303-10 pubmed
    ..These synthetic surfactant preparations may also be a cost-saving therapeutic approach, with better quality control than may be obtained with animal-based treatments. ..
  25. Kandasamy S, Larson R. Molecular dynamics study of the lung surfactant peptide SP-B1-25 with DPPC monolayers: insights into interactions and peptide position and orientation. Biophys J. 2005;88:1577-92 pubmed
    ..The first eight amino acids of the peptide, also known as the insertion sequence, are found to be essential in reducing the fluctuations and anchoring the peptide in the lipid/water interface. ..
  26. Biswas N, Waring A, Walther F, Dluhy R. Structure and conformation of the disulfide bond in dimeric lung surfactant peptides SP-B1-25 and SP-B8-25. Biochim Biophys Acta. 2007;1768:1070-82 pubmed
  27. Wang Y, Rao K, Demchuk E. Topographical organization of the N-terminal segment of lung pulmonary surfactant protein B (SP-B(1-25)) in phospholipid bilayers. Biochemistry. 2003;42:4015-27 pubmed
  28. Griese M, Schumacher S, Tredano M, Steinecker M, Braun A, Guttentag S, et al. Expression profiles of hydrophobic surfactant proteins in children with diffuse chronic lung disease. Respir Res. 2005;6:80 pubmed
  29. Mori K, Ikeda K, Tanaka M. Different expression of surfactant protein B mature peptide and proprotein at 21 weeks' gestation in human fetal pulmonary epithelial cells. Pediatr Int. 2002;44:500-4 pubmed
    ..The production of mature surfactant protein B in terminal airways is scarce at 21 weeks' gestation, which is associated with the immature mechanism of proprotein processing in the cytoplasm. ..
  30. Melton K, Nesslein L, Ikegami M, Tichelaar J, Clark J, Whitsett J, et al. SP-B deficiency causes respiratory failure in adult mice. Am J Physiol Lung Cell Mol Physiol. 2003;285:L543-9 pubmed
    ..Reduction of alveolar SP-B content causes surfactant dysfunction and respiratory failure, indicating that SP-B is required for postnatal lung function. ..
  31. Gortner L, Maroske W, Reiss I, Weller E. Protein- and lipid modification of natural bovine surfactant. Effects in experimental lung failure with special consideration of the response in neonates. Arzneimittelforschung. 2006;56:25-32 pubmed
    ..For the development of surfactant preparations less prone for inactivation the above mentioned data may provide useful information, provided they can be confirmed in further investigations employing other alternative models. ..
  32. Serrano A, Ryan M, Weaver T, Perez Gil J. Critical structure-function determinants within the N-terminal region of pulmonary surfactant protein SP-B. Biophys J. 2006;90:238-49 pubmed
  33. Nesslein L, Melton K, Ikegami M, Na C, Wert S, Rice W, et al. Partial SP-B deficiency perturbs lung function and causes air space abnormalities. Am J Physiol Lung Cell Mol Physiol. 2005;288:L1154-61 pubmed
    ..Chronic, nonuniform SP-B deficiency perturbed pulmonary function and caused air space enlargement. ..
  34. Wert S, Whitsett J, Nogee L. Genetic disorders of surfactant dysfunction. Pediatr Dev Pathol. 2009;12:253-74 pubmed publisher
    ..Mechanisms involved in the pathogenesis of lung disease caused by mutations in these genes will also be discussed...
  35. Grier D, Thompson A, Lappin T, Halliday H. Quantification of Hox and surfactant protein-B transcription during murine lung development. Neonatology. 2009;96:50-60 pubmed publisher
    ..Improved understanding of the genetic processes underlying lung development afforded by our Q-PCR platform may allow development of more specific methods for inducing fetal lung maturation. ..
  36. Miller N, Postle A, Schurch S, Michael Schoel W, Daniels C, Orgeig S. The development of the pulmonary surfactant system in California sea lions. Comp Biochem Physiol A Mol Integr Physiol. 2005;141:191-9 pubmed
    ..The onset of diving is probably a trigger for surfactant development in these animals. ..
  37. Johnston L, Gonzales L, Lightfoot R, Guttentag S, Ischiropoulos H. Opposing regulation of human alveolar type II cell differentiation by nitric oxide and hyperoxia. Pediatr Res. 2010;67:521-5 pubmed publisher
    ..However, hyperoxia overrides these potentially beneficial effects of iNO despite sustained expression of sGC. ..
  38. Wang G, Guo X, Diangelo S, Thomas N, Floros J. Humanized SFTPA1 and SFTPA2 transgenic mice reveal functional divergence of SP-A1 and SP-A2: formation of tubular myelin in vivo requires both gene products. J Biol Chem. 2010;285:11998-2010 pubmed publisher
    ..These observations indicate that SP-A1 and SP-A2 diverged functionally at least in terms of TM formation. ..
  39. Trotter A, Hilgendorff A, Kipp M, Beyer C, Kueppers E, Kiossis E, et al. Gender-related effects of prenatal administration of estrogen and progesterone receptor antagonists on VEGF and surfactant-proteins and on alveolarisation in the developing piglet lung. Early Hum Dev. 2009;85:353-9 pubmed publisher
    ..Estradiol and P antagonism affected gender-related differences of key proteins for pulmonary function and development and especially in males was associated with diminished alveolarisation. ..
  40. Filby C, Hooper S, Sozo F, Zahra V, Flecknoe S, Wallace M. VDUP1: a potential mediator of expansion-induced lung growth and epithelial cell differentiation in the ovine fetus. Am J Physiol Lung Cell Mol Physiol. 2006;290:L250-8 pubmed publisher
    ..803, P<0.0001) and following altered lung expansion (R2=0.817, P<0.001). We suggest that VDUP1 may be an important mediator of expansion-induced lung cell proliferation and AEC differentiation in the developing lung...
  41. Berry G, Wu S, Buccafusca R, Ren J, Gonzales L, Ballard P, et al. Loss of murine Na+/myo-inositol cotransporter leads to brain myo-inositol depletion and central apnea. J Biol Chem. 2003;278:18297-302 pubmed
    ..This model demonstrates the critical importance of SMIT1 in the developing nervous system. The high affinity SMIT1 transporter is responsible for the Ins concentration gradient in the murine fetal-placental unit. ..
  42. Fullagar W, Holt S, Gentle I. Structure of SP-B/DPPC mixed films studied by neutron reflectometry. Biophys J. 2008;95:4829-36 pubmed publisher
    ..At 50 mN m(-1), the subphase is almost completely excluded from the DPPC layer, with the SP-B content significantly reduced. Only a small amount of DPPC appears to be associated with the squeezed out SP-B. ..
  43. Abdel Latif M, Oei J, Ward M, Wills E, Tobias V, Lui K. Galvanised by a respiratory distress diagnosis. Arch Dis Child Educ Pract Ed. 2008;93:112-9 pubmed publisher
  44. Salinas D, Sparkman L, Berhane K, Boggaram V. Nitric oxide inhibits surfactant protein B gene expression in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2003;285:L1153-65 pubmed
    ..These data imply that reduced SP-B expression due to elevated NO levels can contribute to lung injury. ..
  45. Hilgendorff A, Rawer D, Doerner M, Tutdibi E, Ebsen M, Schmidt R, et al. Synthetic and natural surfactant differentially modulate inflammation after meconium aspiration. Intensive Care Med. 2003;29:2247-2254 pubmed publisher
    ..Surfactant administration improved both gas exchange and pulmonary inflammatory cytokine transcription. Mechanisms underlying the differential inflammatory response in both surfactant preparations need to be further addressed. ..
  46. Leiner K, Newman D, Li C, Walsh E, Khosla J, Sannes P. Heparin and fibroblast growth factors affect surfactant protein gene expression in type II cells. Am J Respir Cell Mol Biol. 2006;35:611-8 pubmed
  47. Gutierrez J, Suzara V, Dobbs L. Continuous mechanical contraction modulates expression of alveolar epithelial cell phenotype. Am J Respir Cell Mol Biol. 2003;29:81-7 pubmed
    ..In summary, mechanical contraction favors expression of the type II cell phenotype and inhibits expression of the type I cell phenotype in a time- and amplitude-dependent manner. ..
  48. Robin M, Dong P, Hermans C, Bernard A, Bersten A, Doyle I. Serum levels of CC16, SP-A and SP-B reflect tobacco-smoke exposure in asymptomatic subjects. Eur Respir J. 2002;20:1152-61 pubmed
    ..Their evaluation may allow the effects of tobacco smoke on different levels of the respiratory tract, cellular toxicity and epithelial leakage to be distinguished. ..
  49. Lonergan K, Chari R, DeLeeuw R, Shadeo A, Chi B, Tsao M, et al. Identification of novel lung genes in bronchial epithelium by serial analysis of gene expression. Am J Respir Cell Mol Biol. 2006;35:651-61 pubmed
  50. Hashimoto K, Graham B, Geraci M, Fitzgerald G, Egan K, Zhou W, et al. Signaling through the prostaglandin I2 receptor IP protects against respiratory syncytial virus-induced illness. J Virol. 2004;78:10303-9 pubmed
    ..These results suggest that signaling through IP has antiviral effects while protecting against RSV-induced illness and that PGI(2) is a potential therapeutic target in the treatment of RSV. ..
  51. Coya J, Akinbi H, Sáenz A, Yang L, Weaver T, Casals C. Natural Anti-Infective Pulmonary Proteins: In Vivo Cooperative Action of Surfactant Protein SP-A and the Lung Antimicrobial Peptide SP-BN. J Immunol. 2015;195:1628-36 pubmed publisher
    ..pneumoniae infection. These studies show novel anti-infective pathways that could drive development of new strategies against pulmonary infections. ..
  52. Pavlovic J, Papagaroufalis C, Xanthou M, Liu W, Fan R, Thomas N, et al. Genetic variants of surfactant proteins A, B, C, and D in bronchopulmonary dysplasia. Dis Markers. 2006;22:277-91 pubmed
    ..The data indicate that SP loci are linked to BPD. Studies in different study groups and/or of larger sample size are warranted to confirm these observations and delineate genetic background of BPD subgroups. ..
  53. Kim J, Kim S, Rha K, Kim C, Cho J, Lee C, et al. Expression and localization of surfactant proteins in human nasal epithelium. Am J Physiol Lung Cell Mol Physiol. 2007;292:L879-84 pubmed
    ..We demonstrate that SP-A, SP-B, and SP-D are expressed in human nasal mucosa and cultured NHNE cells. Further study of the functional role of SPs in the upper airway is required. ..