Gene Symbol: Sftpd
Description: surfactant protein D
Alias: SP-D, SPD, pulmonary surfactant-associated protein D, CP4, PSP-D, lung surfactant protein D, pulmonary surfactant protein D, surfactant associated protein D, surfactant, pulmonary-associated protein D
Species: rat
Products:     Sftpd

Top Publications

  1. Lin Z, Floros J. Heterogeneous allele expression of pulmonary SP-D gene in rat large intestine and other tissues. Physiol Genomics. 2002;11:235-43 pubmed
    ..The parent-of-origin does not play a role in SP-D allele-specific expression. However, acquired epigenetic factors, family background, or other factors may contribute to the overall pattern of expression...
  2. Cooley J, McDonald B, Accurso F, Crouch E, REMOLD O DONNELL E. Patterns of neutrophil serine protease-dependent cleavage of surfactant protein D in inflammatory lung disease. J Leukoc Biol. 2008;83:946-55 pubmed publisher
    ..The findings support a pre-eminent role for neutrophil elastase as the critical protease responsible for SP-D depletion in inflammatory lung disease. ..
  3. Yamaguchi H, Soda H, Nakamura Y, Takasu M, Tomonaga N, Nakano H, et al. Serum levels of surfactant protein D predict the anti-tumor activity of gefitinib in patients with advanced non-small cell lung cancer. Cancer Chemother Pharmacol. 2011;67:331-8 pubmed publisher
    ..Serum SP-A levels were not associated with PFS. The present study showed that measurement of serum SP-D levels before treatment in patients with NSCLC may be a new surrogate marker for predicting the response to gefitinib. ..
  4. Haczku A, Atochina E, Tomer Y, Chen H, Scanlon S, Russo S, et al. Aspergillus fumigatus-induced allergic airway inflammation alters surfactant homeostasis and lung function in BALB/c mice. Am J Respir Cell Mol Biol. 2001;25:45-50 pubmed
    ..These changes may contribute significantly to the pathophysiology of Af-induced allergic airway hyperresponsiveness. ..
  5. Guo C, Atochina Vasserman E, Abramova E, Foley J, Zaman A, Crouch E, et al. S-nitrosylation of surfactant protein-D controls inflammatory function. PLoS Biol. 2008;6:e266 pubmed publisher
    ..This represents new insight into both the regulation of protein function by S-nitrosylation and NO's role in innate immunity. ..
  6. Kudo K, Sano H, Takahashi H, Kuronuma K, Yokota S, Fujii N, et al. Pulmonary collectins enhance phagocytosis of Mycobacterium avium through increased activity of mannose receptor. J Immunol. 2004;172:7592-602 pubmed
    ..These results provide compelling evidence that SP-A and SP-D enhance mannose receptor-mediated phagocytosis of M. avium by macrophages. ..
  7. Botas C, Poulain F, Akiyama J, Brown C, Allen L, Goerke J, et al. Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D. Proc Natl Acad Sci U S A. 1998;95:11869-74 pubmed
    ..The findings in the SP-D-deficient mice suggest a role for SP-D in surfactant homeostasis. ..
  8. Atochina E, Beck J, Scanlon S, Preston A, Beers M. Pneumocystis carinii pneumonia alters expression and distribution of lung collectins SP-A and SP-D. J Lab Clin Med. 2001;137:429-39 pubmed
    ..001). We conclude that PCP induces marked elevations in alveolar collectin levels because of increased expression and accumulation of SP-A and SP-D protein in SA surfactant. ..
  9. Borron P, Crouch E, Lewis J, Wright J, Possmayer F, Fraher L. Recombinant rat surfactant-associated protein D inhibits human T lymphocyte proliferation and IL-2 production. J Immunol. 1998;161:4599-603 pubmed
    ..We hypothesize that SP-D can dampen lymphocyte responses to exogenous stimuli and protect the lung against collateral immune-mediated damage. ..

More Information


  1. Savani R, Godinez R, Godinez M, Wentz E, Zaman A, Cui Z, et al. Respiratory distress after intratracheal bleomycin: selective deficiency of surfactant proteins B and C. Am J Physiol Lung Cell Mol Physiol. 2001;281:L685-96 pubmed
    ..We conclude that respiratory distress after bleomycin in rats results from surfactant dysfunction in part secondary to selective downregulation of SP-B and SP-C...
  2. Erpenbeck V, Malherbe D, Sommer S, Schmiedl A, Steinhilber W, Ghio A, et al. Surfactant protein D increases phagocytosis and aggregation of pollen-allergen starch granules. Am J Physiol Lung Cell Mol Physiol. 2005;288:L692-8 pubmed
    ..The modulation of allergen phagocytosis by SP-D might play an important role in allergen clearance from the lung and thereby modulate the allergic inflammation of asthma...
  3. Schleh C, Erpenbeck V, Winkler C, Lauenstein H, Nassimi M, Braun A, et al. Allergen particle binding by human primary bronchial epithelial cells is modulated by surfactant protein D. Respir Res. 2010;11:83 pubmed publisher
    ..In the present study, we investigated the uptake of SPP in human primary epithelial cells and the potential modulation by SP-D. The patho-physiological consequence was evaluated by measurement of pro-inflammatory mediators...
  4. Erpenbeck V, Schmidt R, Gunther A, Krug N, Hohlfeld J. Surfactant protein levels in bronchoalveolar lavage after segmental allergen challenge in patients with asthma. Allergy. 2006;61:598-604 pubmed
    ..This study demonstrates significant alterations of all SPs in BAL fluid after allergen challenge of which SP-C was most closely related to surfactant dysfunction and the degree of the allergic inflammation. ..
  5. Fisher J, Sheftelyevich V, Ho Y, Fligiel S, McCormack F, Korfhagen T, et al. Pulmonary-specific expression of SP-D corrects pulmonary lipid accumulation in SP-D gene-targeted mice. Am J Physiol Lung Cell Mol Physiol. 2000;278:L365-73 pubmed
    ..Marked increases in biologically active tissue and alveolar SP-D do not alter lung morphology, macrophage abundance or structure, or surfactant accumulation...
  6. Sin D, Man S, Marciniuk D, Ford G, Fitzgerald M, Wong E, et al. The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;177:1207-14 pubmed publisher
    ..They do, however, significantly reduce serum SP-D levels. These data suggest that these drugs reduce lung-specific but not generalized biomarkers of systemic inflammation in COPD. ..
  7. Honda Y. [Clinical significance of serum surfactant proteins A and D in idiopathic interstitial pneumonia]. Nihon Kyobu Shikkan Gakkai Zasshi. 1996;34 Suppl:181-5 pubmed
    ..We conclude that measurement of SP-D and SP-A in sera can provide an easily identifiable and useful clinical marker for the diagnosis of IIP, and can be used to predict the disease activity of IIP. ..
  8. Foreman M, Kong X, DeMeo D, Pillai S, Hersh C, Bakke P, et al. Polymorphisms in surfactant protein-D are associated with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2011;44:316-22 pubmed publisher
    ..Surfactant protein-D (SFTPD) is immunomodulatory and essential to host defense...
  9. Russo T, Bartholomew L, Davidson B, Helinski J, Carlino U, Knight P, et al. Total extracellular surfactant is increased but abnormal in a rat model of gram-negative bacterial pneumonia. Am J Physiol Lung Cell Mol Physiol. 2002;283:L655-63 pubmed
    ..In vitro surface cycling studies with calf lung surfactant extract suggested that bacterially derived factors may have contributed in part to the surfactant alterations seen in vivo. ..
  10. Hashimoto J, Takahashi M, Saito A, Murata M, Kurimura Y, Nishitani C, et al. Surfactant Protein A Inhibits Growth and Adherence of Uropathogenic Escherichia coli To Protect the Bladder from Infection. J Immunol. 2017;198:2898-2905 pubmed publisher
    ..SP-A directly bound to uroplakin Ia and competed with FimH for uroplakin Ia binding. These results lead us to conclude that SP-A plays important roles in host defense against UPEC. ..
  11. Salminen A, Vuolteenaho R, Paananen R, Ojaniemi M, Hallman M. Surfactant protein D modulates levels of IL-10 and TNF-? in intrauterine compartments during lipopolysaccharide-induced preterm birth. Cytokine. 2012;60:423-30 pubmed publisher
    ..We conclude that SP-D in fetal and gestational tissues modulates the levels of intrauterine inflammatory mediators involved in preterm birth and may contribute to inflammatory processes related to spontaneous preterm labor. ..
  12. Chen C, Wang L. High-dose vascular endothelial growth factor increases surfactant protein gene expressions in preterm rat lung. Early Hum Dev. 2007;83:581-4 pubmed
    ..These results suggest that VEGF might have potential therapeutic implications in enhancing fetal lung maturation. ..
  13. Sin D, Man S, McWilliams A, Lam S. Surfactant protein D and bronchial dysplasia in smokers at high risk of lung cancer. Chest. 2008;134:582-588 pubmed publisher
    ..Reduced SP-D expression in BAL fluid was associated with the progression of bronchial dysplasia. SP-D levels in BAL fluid may serve as a potential biomarker to identify smokers who are at risk of early lung cancer. ..
  14. Taneva S, Voelker D, Keough K. Adsorption of pulmonary surfactant protein D to phospholipid monolayers at the air-water interface. Biochemistry. 1997;36:8173-9 pubmed
  15. Kingma P, Zhang L, Ikegami M, Hartshorn K, McCormack F, Whitsett J. Correction of pulmonary abnormalities in Sftpd-/- mice requires the collagenous domain of surfactant protein D. J Biol Chem. 2006;281:24496-505 pubmed
    ..was evaluated by expressing a SP-D collagen deletion mutant protein (rSftpdCDM) in wild type and SP-D null mice (Sftpd(-/-)). rSftpdCDM formed disulfide-linked trimers that further oligomerized into higher order structures...
  16. Rynkiewicz M, Wu H, Cafarella T, Nikolaidis N, Head J, Seaton B, et al. Differential Ligand Binding Specificities of the Pulmonary Collectins Are Determined by the Conformational Freedom of a Surface Loop. Biochemistry. 2017;56:4095-4105 pubmed publisher
    ..These studies suggest that flexibility in a key surface loop supports the distinctive lipid binding functions of SP-A, thus contributing to its multiple functions in surfactant structure and regulation, and host defense. ..
  17. Wu H, Kuzmenko A, Wan S, Schaffer L, Weiss A, Fisher J, et al. Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability. J Clin Invest. 2003;111:1589-602 pubmed
  18. Lausen M, Lynch N, Schlosser A, Tornoe I, Saekmose S, Teisner B, et al. Microfibril-associated protein 4 is present in lung washings and binds to the collagen region of lung surfactant protein D. J Biol Chem. 1999;274:32234-40 pubmed
    ..b>Lung surfactant protein D (SP-D) was also purified from lung washings, and calcium-dependent binding was demonstrated between ..
  19. White C, Greene K, Allen C, Shannon J. Elevated expression of surfactant proteins in newborn rats during adaptation to hyperoxia. Am J Respir Cell Mol Biol. 2001;25:51-9 pubmed
    ..Taken together, these data indicate that specific surfactant proteins are upregulated at both the pretranslational and post-translational levels in distal lung epithelium during adaptation to hyperoxia in the newborn rat. ..
  20. Nakane T, Nakamae H, Kamoi H, Koh H, Takeoka Y, Sakamoto E, et al. Prognostic value of serum surfactant protein D level prior to transplant for the development of bronchiolitis obliterans syndrome and idiopathic pneumonia syndrome following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008;42:43-9 pubmed publisher
    ..08). Constitutive serum SP-D level before allo-HSCT may be a useful, noninvasive predictor for the development of BOS/IPS. ..
  21. Thomas N, Fan R, Diangelo S, Hess J, Floros J. Haplotypes of the surfactant protein genes A and D as susceptibility factors for the development of respiratory distress syndrome. Acta Paediatr. 2007;96:985-9 pubmed
    ..Study of haplotypes in complex diseases with both genetic and environmental risk factors may lead to better understanding of these types of diseases. ..
  22. Erpenbeck V, Ziegert M, Cavalet Blanco D, Martin C, Baelder R, Glaab T, et al. Surfactant protein D inhibits early airway response in Aspergillus fumigatus-sensitized mice. Clin Exp Allergy. 2006;36:930-40 pubmed
    ..These data suggest that SP-D not only reduces allergen-induced eosinophilic inflammation and airway hyperresponsiveness but also provides protection against early airway obstruction by inhibition of early mediator release. ..
  23. Schmidt R, Markart P, Ruppert C, Temmesfeld B, Nass R, Lohmeyer J, et al. Pulmonary surfactant in patients with Pneumocystis pneumonia and acquired immunodeficiency syndrome. Crit Care Med. 2006;34:2370-6 pubmed
    ..We analyzed pulmonary surfactant composition and function in bronchoalveolar lavage fluid (BALF) from ventilated and spontaneously breathing HIV-positive patients with PCP...
  24. Schleh C, Rothen Rutishauser B, Blank F, Lauenstein H, Nassimi M, Krug N, et al. Surfactant Protein D modulates allergen particle uptake and inflammatory response in a human epithelial airway model. Respir Res. 2012;13:8 pubmed publisher
    ..These results display a possible mechanism of how SP-D can modulate the inflammatory response to inhaled allergen. ..
  25. Endo S, Sato N, Yaegashi Y, Suzuki Y, Kojika M, Yamada Y, et al. Sivelestat sodium hydrate improves septic acute lung injury by reducing alveolar dysfunction. Res Commun Mol Pathol Pharmacol. 2006;119:53-65 pubmed
    ..Administration of sivelestat was found to reduce alveolar dysfunction and improve respiratory function, and it was suggested that early administration might be useful. ..
  26. Crouch E, Hirche T, Shao B, Boxio R, Wartelle J, Benabid R, et al. Myeloperoxidase-dependent inactivation of surfactant protein D in vitro and in vivo. J Biol Chem. 2010;285:16757-70 pubmed publisher
    ..Thus, MPO-derived oxidants can lead to modifications of SP-D structure with associated alterations in its characteristic aggregating activity. ..
  27. Oberley R, Ault K, Neff T, Khubchandani K, Crouch E, Snyder J. Surfactant proteins A and D enhance the phagocytosis of Chlamydia into THP-1 cells. Am J Physiol Lung Cell Mol Physiol. 2004;287:L296-306 pubmed
    ..In addition, the chlamydial pathogens internalized in the presence of collectins are able to grow and replicate in the THP-1 cells after phagocytosis. ..
  28. Murata M, Otsuka M, Ashida N, Yamada G, Kuronuma K, Chiba H, et al. Surfactant protein D is a useful biomarker for monitoring acute lung injury in rats. Exp Lung Res. 2016;42:314-21 pubmed publisher
    ..The SP-D level is the most useful marker of the severity of lung injuries. These results suggest that the measurement of SP-D levels is an additional tool for monitoring acute lung injuries in rats. ..
  29. Shakoori T, Sin D, Ghafoor F, Bashir S, Bokhari S. Serum surfactant protein D during acute exacerbations of chronic obstructive pulmonary disease. Dis Markers. 2009;27:287-94 pubmed publisher
    ..Our study suggests that serum SP-D levels are increased in patients during exacerbations and may be a potential diagnostic biomarker for COPD exacerbations. ..
  30. Yamashita H, Kobayashi Shibata S, Terahara A, Okuma K, Haga A, Wakui R, et al. Prescreening based on the presence of CT-scan abnormalities and biomarkers (KL-6 and SP-D) may reduce severe radiation pneumonitis after stereotactic radiotherapy. Radiat Oncol. 2010;5:32 pubmed publisher
    ..Therefore, pre-screening before SBRT for an IP shadow in CT and serum KL-6 & SP-D is recommended in the management and treatment of patients with primary or secondary lung tumors. ..
  31. Hoegh S, Voss A, Sorensen G, Høj A, Bendixen C, Junker P, et al. Circulating surfactant protein D is decreased in systemic lupus erythematosus. J Rheumatol. 2009;36:2449-53 pubmed publisher
    ..Genetic analysis did not support an association of the Met11Thr genotype with SLE. These findings suggest that low SP-D, unrelated to conventional disease indicators, represents an aspect of SLE etiopathogenesis. ..
  32. Tecle T, White M, Sorensen G, Gantz D, Kacak N, Holmskov U, et al. Critical role for cross-linking of trimeric lectin domains of surfactant protein D in antiviral activity against influenza A virus. Biochem J. 2008;412:323-9 pubmed publisher
    ..These results show that antiviral activities of SP-D can be reproduced without the N-terminal and collagen domains and that cross-linking of NCRDs is essential for antiviral activity of SP-D with respect to IAV. ..
  33. Funk C, Manzer R, Miura T, Groshong S, Ito Y, Travanty E, et al. Rat respiratory coronavirus infection: replication in airway and alveolar epithelial cells and the innate immune response. J Gen Virol. 2009;90:2956-64 pubmed publisher
  34. Persson A, Chang D, Rust K, Moxley M, Longmore W, Crouch E. Purification and biochemical characterization of CP4 (SP-D), a collagenous surfactant-associated protein. Biochemistry. 1989;28:6361-7 pubmed
    b>CP4 is a collagenous glycoprotein (43 kDa, reduced) synthesized by rat type II pulmonary epithelial cells in primary culture (Persson et al., 1988)...
  35. Fujita M, Shannon J, Ouchi H, Voelker D, Nakanishi Y, Mason R. Serum surfactant protein D is increased in acute and chronic inflammation in mice. Cytokine. 2005;31:25-33 pubmed
    ..These data clarified profile of SP-A and SP-D in acute and chronic inflammation and indicated that serum SP-D can serve as a biomarker of lung inflammation in both acute and chronic lung injury in mice. ..
  36. Jain D, Atochina Vasserman E, Tomer Y, Kadire H, Beers M. Surfactant protein D protects against acute hyperoxic lung injury. Am J Respir Crit Care Med. 2008;178:805-13 pubmed publisher
    ..Local expression of SP-D protects against hyperoxic lung injury through modulation of proinflammatory cytokines and antioxidant enzymatic scavenger systems. ..
  37. Jain D, Atochina Vasserman E, Kadire H, Tomer Y, Inch A, Scott P, et al. SP-D-deficient mice are resistant to hyperoxia. Am J Physiol Lung Cell Mol Physiol. 2007;292:L861-71 pubmed
  38. Yong S, Vuk Pavlovic Z, Standing J, Crouch E, Limper A. Surfactant protein D-mediated aggregation of Pneumocystis carinii impairs phagocytosis by alveolar macrophages. Infect Immun. 2003;71:1662-71 pubmed
    ..Thus, SP-D-mediated aggregation of P. carinii may represent one means by which the organism avoids elimination by the host...
  39. Stapleton R, Dixon A, Parsons P, Ware L, Suratt B. The association between BMI and plasma cytokine levels in patients with acute lung injury. Chest. 2010;138:568-77 pubmed publisher
    ..Mechanisms by which obesity may modulate innate immunity in critical illness are unclear, and future studies should elucidate such mechanisms. ..
  40. Atochina Vasserman E, Gow A, Abramova H, Guo C, Tomer Y, Preston A, et al. Immune reconstitution during Pneumocystis lung infection: disruption of surfactant component expression and function by S-nitrosylation. J Immunol. 2009;182:2277-87 pubmed publisher
    ..This worsening of pulmonary inflammation, in response to persistent Pneumocystis Ags, is mediated by recruitment of effector cells modulated by S-nitrosylated SP-D. ..
  41. Griese M, Steinecker M, Schumacher S, Braun A, Lohse P, Heinrich S. Children with absent surfactant protein D in bronchoalveolar lavage have more frequently pneumonia. Pediatr Allergy Immunol. 2008;19:639-47 pubmed publisher
    ..In contrast, SP-D deficiency due to consumption or failure to up-regulate SP-D may be linked to pulmonary morbidity in children. ..
  42. King B, Kingma P. Surfactant protein D deficiency increases lung injury during endotoxemia. Am J Respir Cell Mol Biol. 2011;44:709-15 pubmed publisher
    ..by intraperitoneal injection of LPS and direct lung injury by intratracheal injection of LPS in wild-type and Sftpd(-/-) mice to elucidate the role of SP-D during ALI/ARDS...
  43. McCormack F, Gibbons R, Ward S, Kuzmenko A, Wu H, Deepe G. Macrophage-independent fungicidal action of the pulmonary collectins. J Biol Chem. 2003;278:36250-6 pubmed
  44. Jounblat R, Clark H, Eggleton P, Hawgood S, Andrew P, Kadioglu A. The role of surfactant protein D in the colonisation of the respiratory tract and onset of bacteraemia during pneumococcal pneumonia. Respir Res. 2005;6:126 pubmed
    ..Our data provides evidence that SP-D has a significant role to play in the clearance of pneumococci during the early stages of infection in both pulmonary sites and blood. ..
  45. Schmiedl A, Luhrmann A, Pabst R, Koslowski R. Increased surfactant protein a and d expression in acute ovalbumin-induced allergic airway inflammation in brown norway rats. Int Arch Allergy Immunol. 2009;148:118-26 pubmed publisher
  46. Lacaze Masmonteil T, Fraslon C, Bourbon J, Raymondjean M, Kahn A. Characterization of the rat pulmonary surfactant protein A promoter. Eur J Biochem. 1992;206:613-23 pubmed
    ..Some of these motifs, specifically protected in DNase 1 footprinting studies, could therefore be involved in the regulation of SP-A gene expression. ..
  47. Deng Y, Tao Z, Kong Y, Xiao B, Chen S, Xu Y, et al. Association between single nucleotide polymorphisms of surfactant protein D and allergic rhinitis in Chinese patients. Tissue Antigens. 2009;73:546-52 pubmed publisher
    ..The present study aimed to investigate whether polymorphisms within the SFTPD gene (Met11Thr, Ala160Thr, and Ser270Thr) are associated with allergic rhinitis...
  48. Zhang L, Ikegami M, Korfhagen T, McCormack F, Yoshida M, Senior R, et al. Neither SP-A nor NH2-terminal domains of SP-A can substitute for SP-D in regulation of alveolar homeostasis. Am J Physiol Lung Cell Mol Physiol. 2006;291:L181-90 pubmed
    ..and 3) rSftpd/a, consisting of NH(2)-terminal and collagenous domains of SP-D with neck domain and CRD of SP-A, in Sftpd(-/-) mice...
  49. 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. ..
  50. Crouch E, Smith K, McDonald B, Briner D, Linders B, McDonald J, et al. Species differences in the carbohydrate binding preferences of surfactant protein D. Am J Respir Cell Mol Biol. 2006;35:84-94 pubmed
    ..Thus, ligand recognition by human SP-D involves a complex interplay between saccharide presentation, the valency of trimeric subunits, and species-specific residues that flank the primary carbohydrate binding site. ..
  51. Wang H, Head J, Kosma P, Brade H, Muller Loennies S, Sheikh S, et al. Recognition of heptoses and the inner core of bacterial lipopolysaccharides by surfactant protein d. Biochemistry. 2008;47:710-20 pubmed
    ..Interactions with the side chain of inner core heptoses provide a potential mechanism for the recognition of diverse types of LPS by SP-D. ..
  52. Madan T, Reid K, Clark H, Singh M, Nayak A, Sarma P, et al. Susceptibility of mice genetically deficient in SP-A or SP-D gene to invasive pulmonary aspergillosis. Mol Immunol. 2010;47:1923-30 pubmed publisher
    ..The results showed that SP-D gene deficient mice are more susceptible to IPA while SP-A gene deficient mice acquire resistance to IPA. ..
  53. Woodworth B, Wood R, Baatz J, Schlosser R. Sinonasal surfactant protein A1, A2, and D gene expression in cystic fibrosis: a preliminary report. Otolaryngol Head Neck Surg. 2007;137:34-8 pubmed
    ..Patients with CF (n = 4) showed significantly increased SPA1 (82-fold), SPA2 (100-fold), and SPD (47-fold) mRNA (P < 0.05) when compared with controls (n = 5)...