Genomes and Genes
pulmonary surfactant associated protein c
Summary: A pulmonary surfactant associated protein that plays a role in alveolar stability by lowering the surface tension at the air-liquid interface. It is a membrane-bound protein that constitutes 1-2% of the pulmonary surfactant mass. Pulmonary surfactant-associated protein C is one of the most hydrophobic peptides yet isolated and contains an alpha-helical domain with a central poly-valine segment that binds to phospholipid bilayers.
- Cameron H, Somaschini M, Carrera P, Hamvas A, Whitsett J, Wert S, et al. A common mutation in the surfactant protein C gene associated with lung disease. J Pediatr. 2005;146:370-5 pubmed..These findings support the hypothesis that the I73T mutation predisposes to or causes lung disease. ..
- Whitsett J, Weaver T. Hydrophobic surfactant proteins in lung function and disease. N Engl J Med. 2002;347:2141-8 pubmed
- 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. ..
- Bachurski C, Yang G, Currier T, Gronostajski R, Hong D. Nuclear factor I/thyroid transcription factor 1 interactions modulate surfactant protein C transcription. Mol Cell Biol. 2003;23:9014-24 pubmed..Taken together, these findings support the hypothesis that NFI family members interact with TTF-1 to regulate type II cell function. ..
- Johnson A, Braidotti P, Pietra G, Russo S, Kabore A, Wang W, et al. Post-translational processing of surfactant protein-C proprotein: targeting motifs in the NH(2)-terminal flanking domain are cleaved in late compartments. Am J Respir Cell Mol Biol. 2001;24:253-63 pubmed
- Augusto L, Synguelakis M, Johansson J, Pedron T, Girard R, Chaby R. Interaction of pulmonary surfactant protein C with CD14 and lipopolysaccharide. Infect Immun. 2003;71:61-7 pubmed..This ability of SP-C to interact with the pattern recognition molecule CD14 extends the possible immunological targets of SP-C to a large panel of microorganisms that can enter the airways. ..
- Bridges J, Wert S, Nogee L, Weaver T. Expression of a human surfactant protein C mutation associated with interstitial lung disease disrupts lung development in transgenic mice. J Biol Chem. 2003;278:52739-46 pubmed..1728 G --> A mutation causes misfolding of the SP-C proprotein with subsequent induction of the unfolded protein response and endoplasmic reticulum-associated degradation pathways ultimately resulting in disrupted lung morphogenesis. ..
- Mulugeta S, Beers M. Surfactant protein C: its unique properties and emerging immunomodulatory role in the lung. Microbes Infect. 2006;8:2317-23 pubmed
- Chibbar R, Shih F, Baga M, Torlakovic E, Ramlall K, Skomro R, et al. Nonspecific interstitial pneumonia and usual interstitial pneumonia with mutation in surfactant protein C in familial pulmonary fibrosis. Mod Pathol. 2004;17:973-80 pubmed..These observations suggest that individuals with this particular mutation in surfactant protein C gene might be at increased risk of interstitial lung disease of variety of types. ..
- Johansson J. Molecular determinants for amyloid fibril formation: lessons from lung surfactant protein C. Swiss Med Wkly. 2003;133:275-82 pubmed
- Lawson W, Grant S, Ambrosini V, Womble K, Dawson E, Lane K, et al. Genetic mutations in surfactant protein C are a rare cause of sporadic cases of IPF. Thorax. 2004;59:977-80 pubmed..Mutations in SFTPC are identified infrequently in this patient population. These findings indicate that SFTPC mutations do not contribute to the pathogenesis of IPF in the majority of sporadic cases. ..
- 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
- ten Brinke A, van Golde L, Batenburg J. Palmitoylation and processing of the lipopeptide surfactant protein C. Biochim Biophys Acta. 2002;1583:253-65 pubmed..This review summarizes these recent developments in the processing and function of SP-C, with particular emphasis on the signals for and role of palmitoylation of SP-C. ..
- Spragg R, Lewis J, Walmrath H, Johannigman J, Bellingan G, Laterre P, et al. Effect of recombinant surfactant protein C-based surfactant on the acute respiratory distress syndrome. N Engl J Med. 2004;351:884-92 pubmed..Patients who received surfactant had a greater improvement in gas exchange during the 24-hour treatment period than patients who received standard therapy alone, suggesting the potential benefit of a longer treatment course. ..
- Tredano M, Griese M, Brasch F, Schumacher S, de Blic J, Marque S, et al. Mutation of SFTPC in infantile pulmonary alveolar proteinosis with or without fibrosing lung disease. Am J Med Genet A. 2004;126A:18-26 pubmed..This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299/suppmat/index.html. ..
- Augusto L, Synguelakis M, Espinassous Q, Lepoivre M, Johansson J, Chaby R. Cellular antiendotoxin activities of lung surfactant protein C in lipid vesicles. Am J Respir Crit Care Med. 2003;168:335-41 pubmed..These results indicate that SP-C may play a role in lung defense; SP-C resists degradation under inflammatory conditions and traps lipopolysaccharide, preventing it from inducing production of noxious mediators in alveolar cells. ..
- 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. ..
- 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. ..
- Glasser S, Burhans M, Eszterhas S, Bruno M, Korfhagen T. Human SP-C gene sequences that confer lung epithelium-specific expression in transgenic mice. Am J Physiol Lung Cell Mol Physiol. 2000;278:L933-45 pubmed..These results suggest that the TTF-1 cis-active sites are important in directing cell-specific expression of the SP-C gene in vivo...
- Zhang X, Han B, Huang J, Zheng B, Geng Q, Aziz F, et al. Prognostic significance of OCT4 expression in adenocarcinoma of the lung. Jpn J Clin Oncol. 2010;40:961-6 pubmed publisher..The cancer cells with bronchioalveolar stem cells phenotype are detectable in adenocarcinoma of the lung and the expression of self-renewal regulatory gene OCT4 in these cells indicated the worse clinical outcomes. ..
- Casals C, Johansson H, Saenz A, Gustafsson M, Alfonso C, Nordling K, et al. C-terminal, endoplasmic reticulum-lumenal domain of prosurfactant protein C - structural features and membrane interactions. FEBS J. 2008;275:536-47 pubmed publisher..The exposed hydrophobic surfaces and the structural disordering that result from interactions with phospholipid membranes suggest a mechanism whereby CTC binds to misfolded SP-C in the endoplasmic reticulum membrane. ..
- Dong M, Bridges J, Apsley K, Xu Y, Weaver T. ERdj4 and ERdj5 are required for endoplasmic reticulum-associated protein degradation of misfolded surfactant protein C. Mol Biol Cell. 2008;19:2620-30 pubmed publisher..ERdj4 and ERdj5 promote turnover of misfolded SP-C and this activity is dependent on their ability to stimulate BiP ATPase activity. ..
- Salminen A, Paananen R, Karjalainen M, Tuohimaa A, Luukkonen A, Ojaniemi M, et al. Genetic association of SP-C with duration of preterm premature rupture of fetal membranes and expression in gestational tissues. Ann Med. 2009;41:629-42 pubmed publisher..SFTPC SNP rs4715 associates with the duration of PPROM, and SP-C is expressed in gestational tissues. We propose that fetal SFTPC moderates the inflammatory activation within the fetal extra-embryonic compartment. ..
- 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. ..
- Loyd J. Pulmonary fibrosis in families. Am J Respir Cell Mol Biol. 2003;29:S47-50 pubmed
- 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. ..
- Kabore A, Wang W, Russo S, Beers M. Biosynthesis of surfactant protein C: characterization of aggresome formation by EGFP chimeras containing propeptide mutants lacking conserved cysteine residues. J Cell Sci. 2001;114:293-302 pubmed..Mutation or deletion of one or both of these residues results in misfolding with mistargeting of unprocessed mutant protein, leading to formation of stable aggregates within aggresomes. ..
- 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...
- Glasser S, Senft A, Whitsett J, Maxfield M, Ross G, Richardson T, et al. Macrophage dysfunction and susceptibility to pulmonary Pseudomonas aeruginosa infection in surfactant protein C-deficient mice. J Immunol. 2008;181:621-8 pubmed..SP-C plays an important role in innate host defense of the lung, enhancing macrophage-mediated Pseudomonas phagocytosis, clearance and limiting pulmonary inflammatory responses. ..
- Soraisham A, Tierney A, Amin H. Neonatal respiratory failure associated with mutation in the surfactant protein C gene. J Perinatol. 2006;26:67-70 pubmed..This particular SFTPC mutation is novel, and the infant's lung disease was unusually severe compared to what has been previously reported in association with SFTPC mutations. ..
- Yang Y, Yang M, Guo Y, Williams O, Weissler J. PLAGL2 expression-induced lung epithelium damages at bronchiolar alveolar duct junction in emphysema: bNip3- and SP-C-associated cell death/injury activity. Am J Physiol Lung Cell Mol Physiol. 2009;297:L455-66 pubmed publisher..In summary, our data from both animal and human studies support a novel pathogenic role of PLAGL2 in pulmonary emphysema, a critical aspect of severe COPD. ..
- 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. ..
- Kramer B, Jobe A, Ikegami M. Monocyte function in preterm, term, and adult sheep. Pediatr Res. 2003;54:52-7 pubmed..The reduced phagocytosis of apoptotic cells by monocytes from the preterm may contribute to prolonged inflammation in diseases such as bronchopulmonary dysplasia. ..
- 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. ..
- Almlén A, Stichtenoth G, Robertson B, Johansson J, Curstedt T. Concentration dependence of a poly-leucine surfactant protein C analogue on in vitro and in vivo surfactant activity. Neonatology. 2007;92:194-200 pubmed
- Phokela S, Peleg S, Moya F, Alcorn J. Regulation of human pulmonary surfactant protein gene expression by 1alpha,25-dihydroxyvitamin D3. Am J Physiol Lung Cell Mol Physiol. 2005;289:L617-26 pubmed
- Dohm M, Brown N, Seurynck Servoss S, Bernardino de la Serna J, Barron A. Mimicking SP-C palmitoylation on a peptoid-based SP-B analogue markedly improves surface activity. Biochim Biophys Acta. 2010;1798:1663-78 pubmed publisher..N-terminus alkylation may be a simple, effective method for increasing lipid affinity and surface activity of single-helix SP-B mimics. ..
- Knebel D, Sieber M, Reichelt R, Galla H, Amrein M. Fluorescence light microscopy of pulmonary surfactant at the air-water interface of an air bubble of adjustable size. Biophys J. 2002;83:547-55 pubmed..In the lung, such multilayer phase acts as a reservoir that guarantees a full molecular coverage of the alveolar interface during the breathing cycle and provides mechanical stability to the film. ..
- Headley M, Zhou B, Shih W, Aye T, Comeau M, Ziegler S. TSLP conditions the lung immune environment for the generation of pathogenic innate and antigen-specific adaptive immune responses. J Immunol. 2009;182:1641-7 pubmed..This study provides new insight into the unique features of the asthma pathology contributed by the innate and adaptive immune responses in response to TSLP stimulation. ..
- Morimoto M, Kopan R. rtTA toxicity limits the usefulness of the SP-C-rtTA transgenic mouse. Dev Biol. 2009;325:171-8 pubmed publisher..These studies demonstrate the importance of using appropriate SP-C-rtTA only controls in all experiments. ..
- Hyatt B, Resnik E, Johnson N, Lohr J, Cornfield D. Lung specific developmental expression of the Xenopus laevis surfactant protein C and B genes. Gene Expr Patterns. 2007;7:8-14 pubmed..laevis, xSP-C and xSP-B are expressed only in lung. Knowledge of the sequence and expression pattern of these two surfactant proteins in Xenopus might allow for use of this organism to study early lung development. ..
- Szczawińska Popłonyk A, Breborowicz A, Langfort R. [Interstitial lung disease associated with surfactant protein B and C deficiencies]. Pneumonol Alergol Pol. 2010;78:224-8 pubmed..In the paper clinical manifestation, radiological findings, molecular background and prognosis in interstitial lung diseases associated with SP-B and SP-C defects have been discussed...
- Hosia W, Johansson J, Griffiths W. Hydrogen/deuterium exchange and aggregation of a polyvaline and a polyleucine alpha-helix investigated by matrix-assisted laser desorption ionization mass spectrometry. Mol Cell Proteomics. 2002;1:592-7 pubmed..The SP-C helix, but not the SP-C(Leu) helix, is thus in a metastable state, which may contribute to the recently observed tendency of SP-C and its precursor to misfold and aggregate in vivo. ..
- Gruh I, Wunderlich S, Winkler M, Schwanke K, Heinke J, Blomer U, et al. Human CMV immediate-early enhancer: a useful tool to enhance cell-type-specific expression from lentiviral vectors. J Gene Med. 2008;10:21-32 pubmed..g. to analyze stem cell differentiation in transplantation and co-culture settings. ..
- Pfister R, Soll R. New synthetic surfactants: the next generation?. Biol Neonate. 2005;87:338-44 pubmed..Clinicians will need to further understand any differences in clinical effects between available products. ..
- Duan W, Ding H, Subler M, Zhu W, Zhang H, Stoner G, et al. Lung-specific expression of human mutant p53-273H is associated with a high frequency of lung adenocarcinoma in transgenic mice. Oncogene. 2002;21:7831-8 pubmed
- Amato M, Petit K, Fiore H, Doyle C, Frantz I, Nielsen H. Effect of exogenous surfactant on the development of surfactant synthesis in premature rabbit lung. Pediatr Res. 2003;53:671-8 pubmed..We conclude that surfactant replacement therapy can enhance the maturation of surfactant synthesis, but this potential benefit differs with different surfactant preparations. ..
- Na Nakorn P, Meyer M, Flach C, Mendelsohn R, Galla H. Surfactant protein C and lung function: new insights into the role of alpha-helical length and palmitoylation. Eur Biophys J. 2007;36:477-89 pubmed..Palmitoylation obviously mediates interactions between lipids and/or peptides not only within a protein/lipid film but also between neighbouring layers and induces a stacking of bilayers. ..
- Tashiro K, Ohta K, Cui X, Nishizuka K, Yamamoto K, Konzaki T, et al. Effects of various forms of surfactant protein C on tidal volume in ventilated immature newborn rabbits. J Appl Physiol (1985). 2003;94:1519-26 pubmed..The physiological effect of basic mixture was not improved by monomeric SP-C. We conclude that palmitoyl groups are important for the physiological effects of SP-C and that the dimeric form also improves physiological effects. ..
- Lyra P, Diniz E. The importance of surfactant on the development of neonatal pulmonary diseases. Clinics (Sao Paulo). 2007;62:181-90 pubmed