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Gene Review

Sftpd  -  surfactant associated protein D

Mus musculus

Synonyms: AI573415, Lung surfactant protein D, PSP-D, Pulmonary surfactant-associated protein D, SP-D, ...
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Disease relevance of Sftpd

  • NH(2)-rSftpa/d did not correct emphysema, foamy macrophage and lymphocyte infiltration, or the increased lipid accumulations characteristic of Sftpd(-/-) mice [1].
  • Susceptibility of mice genetically deficient in the surfactant protein (SP)-A or SP-D gene to pulmonary hypersensitivity induced by antigens and allergens of Aspergillus fumigatus [2].
  • SP-D deficiency results in multiple abnormalities in surfactant forms and metabolism that cannot be attributed to a single mechanism [3].
  • Both serum and lung SP-D concentrations were increased in chronic lung inflammation [4].
  • Since the airway is the usual portal of entry for influenza A virus and other respiratory pathogens, SP-D is likely to play an important role in innate defense responses to IAV [5].

Psychiatry related information on Sftpd

  • The hydrophilic surfactant proteins A (SP-A) and D (SP-D) play important roles in host defense mechanisms of the lung [6].

High impact information on Sftpd

  • Surfactant proteins A and D (SP-A and SP-D) are lung collectins composed of two regions, a globular head domain that binds PAMPs and a collagenous tail domain that initiates phagocytosis [7].
  • The pulmonary collectins, surfactant proteins A (SP-A) and D (SP-D), have been reported to bind lipopolysaccharide (LPS), opsonize microorganisms, and enhance the clearance of lung pathogens [8].
  • These data indicate that SP-A and SP-D are antimicrobial proteins that directly inhibit the proliferation of Gram-negative bacteria in a macrophage- and aggregation-independent manner by increasing the permeability of the microbial cell membrane [8].
  • These results clearly implicate pulmonary SP-A and SP-D in the modulation of allergic reactions [9].
  • Lung surfactant proteins SP-A and SP-D can interact with the glycosylated antigens and allergens of AFU:, inhibit specific IgE binding to these allergens, and block histamine release from sensitized basophils [9].

Chemical compound and disease context of Sftpd


Biological context of Sftpd

  • An NFAT-dependent enhancer modulated by NFATs or calcineurin and sensitive to cyclosporin was identified in the Sftpd promoter [13].
  • Three new polymorphic microsatellites are also described, one of which is just 160 base pairs upstream of Sftpd [14].
  • An atypical, rodent-specific, long terminal repeat of retroviral origin containing a minisatellite that has become inserted in Sftpd is described [14].
  • The findings in the SP-D-deficient mice suggest a role for SP-D in surfactant homeostasis [15].
  • On the basis of homology with other collectins, potential functions for SP-D include roles in innate immunity and surfactant metabolism [15].

Anatomical context of Sftpd

  • Here, we identify a role of nuclear factor of activated T cells (NFATs) in regulation of murine SP-D gene (Sftpd) transcription [13].
  • Nuclear factor of activated T cells regulates transcription of the surfactant protein D gene (Sftpd) via direct interaction with thyroid transcription factor-1 in lung epithelial cells [13].
  • SP-D plays a critical role in the suppression of alveolar macrophage activation, which may contribute to the pathogenesis of chronic inflammation and emphysema [16].
  • The SP-D gene was disrupted in embryonic stem cells by homologous recombination to generate mice deficient in SP-D [15].
  • Surfactant protein D (SP-D) is one of two collectins found in the pulmonary alveolus [15].

Associations of Sftpd with chemical compounds


Physical interactions of Sftpd

  • 1,3-beta-Glucan was a good stimulator of BAM for TNF-alpha production and was detected on B. dermatitidis by IFA. beta-Glucan incubated with BALF inhibited the binding of SP-D in BALF to B. dermatitidis as demonstrated by IFA [21].
  • Increased NF-kappaB binding was detected by EMSA in nuclear extracts of AMs isolated from SP-D(-/-) mice [19].

Enzymatic interactions of Sftpd


Regulatory relationships of Sftpd


Other interactions of Sftpd

  • The increased sCD14 seen in SP-D-/- mice was dependent upon the activation of MMP-12 via an MMP-9-dependent mechanism [24].
  • In conclusion, SP-D influences innate host defense, in part, by regulating sCD14 in a process mediated by MMP-9 and MMP-12 [24].
  • CD14 was reduced on alveolar macrophages from SP-D-/- mice and was associated with reduced uptake of LPS and decreased production of TNF-alpha after LPS stimulation [24].
  • Whereas alveolar and tissue surfactant phospholipid pools were increased, levels of other surfactant proteins were not altered (SP-B) or were modestly increased (SP-A and SP-D) [25].
  • Surfactant proteins-A and -D (SP-A and SP-D) are members of the collectin protein family [26].

Analytical, diagnostic and therapeutic context of Sftpd

  • Soluble CD14 (sCD14) was increased in the bronchoalveolar lavage fluid from SP-D-/- mice [24].
  • Human lung and stomach, but not heart or liver, were found to express SP-D mRNA, as determined by PCR [27].
  • Northern blot and RT-PCR analysis revealed that the mouse SP-D gene is expressed predominantly in lung and, surprisingly, also in heart, stomach, and kidney but not in brain [27].
  • Porcine SP-D will also be an important reagent for use in existing porcine animal models for human lung infections [28].
  • Late isolates were shown to be much more sensitive than early strains to neutralization by the mouse serum mannose-binding lectin (MBL) and rat lung surfactant protein D (SP-D) and bound greater levels of these lectins in enzyme-linked immunosorbent assays and Western blot analyses [29].


  1. Neither SP-A nor NH2-terminal domains of SP-A can substitute for SP-D in regulation of alveolar homeostasis. Zhang, L., Ikegami, M., Korfhagen, T.R., McCormack, F.X., Yoshida, M., Senior, R.M., Shipley, J.M., Shapiro, S.D., Whitsett, J.A. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  2. Susceptibility of mice genetically deficient in the surfactant protein (SP)-A or SP-D gene to pulmonary hypersensitivity induced by antigens and allergens of Aspergillus fumigatus. Madan, T., Reid, K.B., Singh, M., Sarma, P.U., Kishore, U. J. Immunol. (2005) [Pubmed]
  3. Surfactant metabolism in SP-D gene-targeted mice. Ikegami, M., Whitsett, J.A., Jobe, A., Ross, G., Fisher, J., Korfhagen, T. Am. J. Physiol. Lung Cell Mol. Physiol. (2000) [Pubmed]
  4. Serum surfactant protein D is increased in acute and chronic inflammation in mice. Fujita, M., Shannon, J.M., Ouchi, H., Voelker, D.R., Nakanishi, Y., Mason, R.J. Cytokine (2005) [Pubmed]
  5. Surfactant protein D enhances clearance of influenza A virus from the lung in vivo. LeVine, A.M., Whitsett, J.A., Hartshorn, K.L., Crouch, E.C., Korfhagen, T.R. J. Immunol. (2001) [Pubmed]
  6. The lung collectins, SP-A and SP-D, modulate pulmonary innate immunity. Sano, H., Kuroki, Y. Mol. Immunol. (2005) [Pubmed]
  7. By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation. Gardai, S.J., Xiao, Y.Q., Dickinson, M., Nick, J.A., Voelker, D.R., Greene, K.E., Henson, P.M. Cell (2003) [Pubmed]
  8. Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability. Wu, H., Kuzmenko, A., Wan, S., Schaffer, L., Weiss, A., Fisher, J.H., Kim, K.S., McCormack, F.X. J. Clin. Invest. (2003) [Pubmed]
  9. Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens. Madan, T., Kishore, U., Singh, M., Strong, P., Clark, H., Hussain, E.M., Reid, K.B., Sarma, P.U. J. Clin. Invest. (2001) [Pubmed]
  10. Nucleic acid is a novel ligand for innate, immune pattern recognition collectins surfactant proteins A and D and mannose-binding lectin. Palaniyar, N., Nadesalingam, J., Clark, H., Shih, M.J., Dodds, A.W., Reid, K.B. J. Biol. Chem. (2004) [Pubmed]
  11. Surfactant protein D inhibits early airway response in Aspergillus fumigatus-sensitized mice. Erpenbeck, V.J., Ziegert, M., Cavalet-Blanco, D., Martin, C., Baelder, R., Glaab, T., Braun, A., Steinhilber, W., Luettig, B., Uhlig, S., Hoymann, H.G., Krug, N., Hohlfeld, J.M. Clin. Exp. Allergy (2006) [Pubmed]
  12. Role of surfactant protein D (SP-D) in innate immunity in the gastric mucosa: evidence of interaction with Helicobacter pylori lipopolysaccharide. Moran, A.P., Khamri, W., Walker, M.M., Thursz, M.R. J. Endotoxin Res. (2005) [Pubmed]
  13. Nuclear factor of activated T cells regulates transcription of the surfactant protein D gene (Sftpd) via direct interaction with thyroid transcription factor-1 in lung epithelial cells. Davé, V., Childs, T., Whitsett, J.A. J. Biol. Chem. (2004) [Pubmed]
  14. Genomic organization of the mouse gene for lung surfactant protein D. Lawson, P.R., Perkins, V.C., Holmskov, U., Reid, K.B. Am. J. Respir. Cell Mol. Biol. (1999) [Pubmed]
  15. Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D. Botas, C., Poulain, F., Akiyama, J., Brown, C., Allen, L., Goerke, J., Clements, J., Carlson, E., Gillespie, A.M., Epstein, C., Hawgood, S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  16. Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice. Wert, S.E., Yoshida, M., LeVine, A.M., Ikegami, M., Jones, T., Ross, G.F., Fisher, J.H., Korfhagen, T.R., Whitsett, J.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  17. Reversibility of pulmonary abnormalities by conditional replacement of surfactant protein D (SP-D) in vivo. Zhang, L., Ikegami, M., Dey, C.R., Korfhagen, T.R., Whitsett, J.A. J. Biol. Chem. (2002) [Pubmed]
  18. Surfactant protein-D regulates surfactant phospholipid homeostasis in vivo. Korfhagen, T.R., Sheftelyevich, V., Burhans, M.S., Bruno, M.D., Ross, G.F., Wert, S.E., Stahlman, M.T., Jobe, A.H., Ikegami, M., Whitsett, J.A., Fisher, J.H. J. Biol. Chem. (1998) [Pubmed]
  19. Surfactant protein D regulates NF-kappa B and matrix metalloproteinase production in alveolar macrophages via oxidant-sensitive pathways. Yoshida, M., Korfhagen, T.R., Whitsett, J.A. J. Immunol. (2001) [Pubmed]
  20. Surfactant protein A and D differently regulate the immune response to nonmucoid Pseudomonas aeruginosa and its lipopolysaccharide. Bufler, P., Schmidt, B., Schikor, D., Bauernfeind, A., Crouch, E.C., Griese, M. Am. J. Respir. Cell Mol. Biol. (2003) [Pubmed]
  21. Effect of lung surfactant collectins on bronchoalveolar macrophage interaction with Blastomyces dermatitidis: inhibition of tumor necrosis factor alpha production by surfactant protein D. Lekkala, M., LeVine, A.M., Linke, M.J., Crouch, E.C., Linders, B., Brummer, E., Stevens, D.A. Infect. Immun. (2006) [Pubmed]
  22. Surfactant protein D binds genomic DNA and apoptotic cells, and enhances their clearance, in vivo. Palaniyar, N., Clark, H., Nadesalingam, J., Hawgood, S., Reid, K.B. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  23. Surfactant protein D deficiency influences allergic immune responses. Schaub, B., Westlake, R.M., He, H., Arestides, R., Haley, K.J., Campo, M., Velasco, G., Bellou, A., Hawgood, S., Poulain, F.R., Perkins, D.L., Finn, P.W. Clin. Exp. Allergy (2004) [Pubmed]
  24. Surfactant protein-D regulates soluble CD14 through matrix metalloproteinase-12. Senft, A.P., Korfhagen, T.R., Whitsett, J.A., Shapiro, S.D., LeVine, A.M. J. Immunol. (2005) [Pubmed]
  25. Pneumonitis and emphysema in sp-C gene targeted mice. Glasser, S.W., Detmer, E.A., Ikegami, M., Na, C.L., Stahlman, M.T., Whitsett, J.A. J. Biol. Chem. (2003) [Pubmed]
  26. Sequential targeted deficiency of SP-A and -D leads to progressive alveolar lipoproteinosis and emphysema. Hawgood, S., Ochs, M., Jung, A., Akiyama, J., Allen, L., Brown, C., Edmondson, J., Levitt, S., Carlson, E., Gillespie, A.M., Villar, A., Epstein, C.J., Poulain, F.R. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  27. Mouse surfactant protein-D. cDNA cloning, characterization, and gene localization to chromosome 14. Motwani, M., White, R.A., Guo, N., Dowler, L.L., Tauber, A.I., Sastry, K.N. J. Immunol. (1995) [Pubmed]
  28. Porcine lung surfactant protein D: complementary DNA cloning, chromosomal localization, and tissue distribution. van Eijk, M., Haagsman, H.P., Skinner, T., Archibald, A., Reid, K.B., Lawson, P.R., Archibold, A. J. Immunol. (2000) [Pubmed]
  29. Collectin-mediated antiviral host defense of the lung: evidence from influenza virus infection of mice. Reading, P.C., Morey, L.S., Crouch, E.C., Anders, E.M. J. Virol. (1997) [Pubmed]
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