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Gene Review

SFTPD  -  surfactant protein D

Homo sapiens

Synonyms: COLEC7, Collectin-7, Lung surfactant protein D, PSP-D, PSPD, ...
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Disease relevance of SFTPD


Psychiatry related information on SFTPD

  • Increasing evidence suggests that surfactant components, in particular the hydrophilic surfactant proteins SP-A and SP-D, play potentially important roles in host defense mechanisms [6].

High impact information on SFTPD

  • The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung [7].
  • Neutrophil dysfunction resulting from IAV exposure was diminished when the virus was pre-incubated with SP-D [2].
  • SP-D enhanced neutrophil binding of IAV and neutrophil respiratory burst responses to the virus [2].
  • SP-D potently inhibited hemagglutination activity of several strains of IAV as well as causing viral aggregation [2].
  • Surfactant protein D (SP-D) is a collagenous glycoprotein that is secreted into the pulmonary airspaces by alveolar type II and nonciliated bronchiolar cells [8].

Chemical compound and disease context of SFTPD


Biological context of SFTPD

  • Surfactant protein D (SP-D) is an oligomeric C type lectin that promotes phagocytosis by binding to microbial surface carbohydrates [14].
  • Lung surfactant protein-D (SP-D), a collectin mainly produced by alveolar type II cells, initiates the effector mechanisms of innate immunity on binding to microbial carbohydrates [15].
  • Surfactant protein D (SP-D) plays roles in pulmonary host defense and surfactant homeostasis and is increased following acute lung injury [4].
  • Segregation analysis of HindIII digests of genomic DNA using specific cDNA probes demonstrated selective hybridization of radiolabeled hSP-D cDNA to chromosome 10- and 10q-containing human/hamster somatic hybrids [16].
  • Gel filtration chromatography revealed two distinct m.w. peaks with SP-D immunoreactivity in serum from Met/Met(11)-encoding genotypes [17].

Anatomical context of SFTPD

  • The distribution of gp-340 in macrophages is compatible with a role as an opsonin receptor for SP-D [14].
  • SP-D is secreted into the pulmonary airspaces by lung epithelial cells and is believed to contribute to the lung's defense against inhaled microorganisms [16].
  • Rat alveolar macrophages that had been incubated with SP-A or SP-D also exhibited enhanced uptake of (125)I-mannosylated BSA [18].
  • Here we describe the co-purification of decorin, a novel SP-D-binding protein, from amniotic fluid [19].
  • The localization and functions of SP-D indicate that this collectin is the counterpart in the innate immune system of IgA in the adaptive immune system [15].

Associations of SFTPD with chemical compounds

  • A 340-kDa glycoprotein (gp-340) has been shown to bind SP-D in the presence of calcium but does so independently of carbohydrate recognition [14].
  • Human proteinosis SP-D was extracted from the 10,000 x g pellet of bronchoalveolar lavage with 100 mmol/L glucose or ethylenediamine tetraacetic acid, and specifically bound to and eluted from maltosyl-agarose [20].
  • The binding between SP-D and mannan also required the presence of calcium, but this interaction was completely inhibited by maltose [21].
  • Rat and human SP-D bound the organism with high affinity in a reaction that required Ca(2+) and was inhibited by EGTA [22].
  • Mannose, glucose, maltose, and inositol, at millimolar concentrations, competed for human SP-D binding to the bacterial membrane [22].
  • SP-D significantly reduced MD-2 binding to both serotypes of LPS [23].

Physical interactions of SFTPD

  • The human decorin that co-purified with SP-D is a 130-150-kDa proteoglycan, which has a 46-kDa protein core and approximately 90-kDa dermatan sulfate chain [19].
  • Structural superimposition of hSP-D with mannose- binding protein C (MBP-C) complexed with GlcNAc reveals steric clashes between the ligand and the side chain of Arg343 in hSP-D [24].
  • SP-A and SP-D also bind lipids and SP-A is involved in organization of alveolar surfactant phospholipids [25].
  • The pulmonary surfactant proteins SP-A and SP-D as well as the serum collectins mannose-binding protein and CL-43 bound in a calcium-dependent manner to acapsular C. neoformans in vitro [26].

Regulatory relationships of SFTPD


Other interactions of SFTPD

  • The same binding pattern was seen between gp-340 and recombinant human SP-D composed of the trimeric neck region and three carbohydrate recognition domains [21].
  • In contrast to lung surfactant protein D (SP-D), which is generally expressed on mucosal surfaces, SP-A seems to be restricted to the respiratory system [31].
  • SP-A belongs to the family of collagenous C-type lectins along with mannose binding protein (MBP) and SP-D, both of which have also been mapped to the long arm of chromosome 10 [32].
  • No cDNA segment of SP-B, SP-C, or SP-D cDNA was amplified from isolated submucosal glands or superficial epithelial cells, whereas all were amplified from alveolar tissue [33].
  • The relative location of SP-A2 and SP-D was then ascertained by testing a number of sequence tagged sites against the Stanford TNG3 and G3 radiation hybrid panels [32].

Analytical, diagnostic and therapeutic context of SFTPD

  • SP-D was shown to contribute to potent anti-IAV activity of human bronchoalveolar lavage fluid [2].
  • SP-D from both peaks bound to mannan-coated ELISA plates [17].
  • When chromatographed on 4% agarose (A-15M) in the presence of ethylenediamine tetraacetic acid, the solubilized human proteinosis SP-D eluted near the void volume and earlier than rat SP-D dodecamers or human SP-D multimers in the lavage supernatant [20].
  • A panel of mRNAs from human tissues was screened for SP-D mRNA by RT-PCR [15].
  • Lipids extracted from membranes and separated by two-dimensional thin layer chromatography bound human SP-D with high affinity in a Ca(2+)-dependent reaction [22].


  1. Polymorphisms in the human surfactant protein-D (SFTPD) gene: strong evidence that serum levels of surfactant protein-D (SP-D) are genetically influenced. Heidinger, K., König, I.R., Bohnert, A., Kleinsteiber, A., Hilgendorff, A., Gortner, L., Ziegler, A., Chakraborty, T., Bein, G. Immunogenetics (2005) [Pubmed]
  2. Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses. Hartshorn, K.L., Crouch, E.C., White, M.R., Eggleton, P., Tauber, A.I., Chang, D., Sastry, K. J. Clin. Invest. (1994) [Pubmed]
  3. Degradation of pulmonary surfactant protein D by Pseudomonas aeruginosa elastase abrogates innate immune function. Alcorn, J.F., Wright, J.R. J. Biol. Chem. (2004) [Pubmed]
  4. Surfactant protein D gene regulation. Interactions among the conserved CCAAT/enhancer-binding protein elements. He, Y., Crouch, E. J. Biol. Chem. (2002) [Pubmed]
  5. Surfactant protein D binds selectively to Klebsiella pneumoniae lipopolysaccharides containing mannose-rich O-antigens. Sahly, H., Ofek, I., Podschun, R., Brade, H., He, Y., Ullmann, U., Crouch, E. J. Immunol. (2002) [Pubmed]
  6. Potential role of surfactant proteins A and D in innate lung defense against pathogens. van Golde, L.M. Biol. Neonate (1995) [Pubmed]
  7. The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung. McCormack, F.X., Whitsett, J.A. J. Clin. Invest. (2002) [Pubmed]
  8. Interactions of surfactant protein D with bacterial lipopolysaccharides. Surfactant protein D is an Escherichia coli-binding protein in bronchoalveolar lavage. Kuan, S.F., Rust, K., Crouch, E. J. Clin. Invest. (1992) [Pubmed]
  9. Surfactant protein D gene polymorphism associated with severe respiratory syncytial virus infection. Lahti, M., Lofgren, J., Marttila, R., Renko, M., Klaavuniemi, T., Haataja, R., Ramet, M., Hallman, M. Pediatr. Res. (2002) [Pubmed]
  10. Protective role of lung surfactant protein D in a murine model of invasive pulmonary aspergillosis. Madan, T., Kishore, U., Singh, M., Strong, P., Hussain, E.M., Reid, K.B., Sarma, P.U. Infect. Immun. (2001) [Pubmed]
  11. Interaction of human lung surfactant proteins A and D with mite (Dermatophagoides pteronyssinus) allergens. Wang, J.Y., Kishore, U., Lim, B.L., Strong, P., Reid, K.B. Clin. Exp. Immunol. (1996) [Pubmed]
  12. Surfactant protein A enhances the binding and deacylation of E. coli LPS by alveolar macrophages. Stamme, C., Wright, J.R. Am. J. Physiol. (1999) [Pubmed]
  13. Gefitinib-induced interstitial lung disease showing improvement after cessation: disassociation of serum markers. Kitajima, H., Takahashi, H., Harada, K., Kanai, A., Inomata, S., Taniguchi, H., Saikai, T., Abe, S. Respirology (2006) [Pubmed]
  14. Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D. Holmskov, U., Mollenhauer, J., Madsen, J., Vitved, L., Gronlund, J., Tornoe, I., Kliem, A., Reid, K.B., Poustka, A., Skjodt, K. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  15. Localization of lung surfactant protein D on mucosal surfaces in human tissues. Madsen, J., Kliem, A., Tornoe, I., Skjodt, K., Koch, C., Holmskov, U. J. Immunol. (2000) [Pubmed]
  16. Genomic organization of human surfactant protein D (SP-D). SP-D is encoded on chromosome 10q22.2-23.1. Crouch, E., Rust, K., Veile, R., Donis-Keller, H., Grosso, L. J. Biol. Chem. (1993) [Pubmed]
  17. A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D. Leth-Larsen, R., Garred, P., Jensenius, H., Meschi, J., Hartshorn, K., Madsen, J., Tornoe, I., Madsen, H.O., Sørensen, G., Crouch, E., Holmskov, U. J. Immunol. (2005) [Pubmed]
  18. Pulmonary collectins enhance phagocytosis of Mycobacterium avium through increased activity of mannose receptor. Kudo, K., Sano, H., Takahashi, H., Kuronuma, K., Yokota, S., Fujii, N., Shimada, K., Yano, I., Kumazawa, Y., Voelker, D.R., Abe, S., Kuroki, Y. J. Immunol. (2004) [Pubmed]
  19. Identification and characterization of a novel interaction between pulmonary surfactant protein D and decorin. Nadesalingam, J., Bernal, A.L., Dodds, A.W., Willis, A.C., Mahoney, D.J., Day, A.J., Reid, K.B., Palaniyar, N. J. Biol. Chem. (2003) [Pubmed]
  20. Accumulation of surfactant protein D in human pulmonary alveolar proteinosis. Crouch, E., Persson, A., Chang, D. Am. J. Pathol. (1993) [Pubmed]
  21. Isolation and characterization of a new member of the scavenger receptor superfamily, glycoprotein-340 (gp-340), as a lung surfactant protein-D binding molecule. Holmskov, U., Lawson, P., Teisner, B., Tornoe, I., Willis, A.C., Morgan, C., Koch, C., Reid, K.B. J. Biol. Chem. (1997) [Pubmed]
  22. Human surfactant protein D (SP-D) binds Mycoplasma pneumoniae by high affinity interactions with lipids. Chiba, H., Pattanajitvilai, S., Evans, A.J., Harbeck, R.J., Voelker, D.R. J. Biol. Chem. (2002) [Pubmed]
  23. Pulmonary surfactant protein D inhibits lipopolysaccharide (LPS)-induced inflammatory cell responses by altering LPS binding to its receptors. Yamazoe, M., Nishitani, C., Takahashi, M., Katoh, T., Ariki, S., Shimizu, T., Mitsuzawa, H., Sawada, K., Voelker, D.R., Takahashi, H., Kuroki, Y. J. Biol. Chem. (2008) [Pubmed]
  24. Arg343 in human surfactant protein D governs discrimination between glucose and N-acetylglucosamine ligands. Allen, M.J., Laederach, A., Reilly, P.J., Mason, R.J., Voelker, D.R. Glycobiology (2004) [Pubmed]
  25. Molecular structures and interactions of pulmonary surfactant components. Johansson, J., Curstedt, T. Eur. J. Biochem. (1997) [Pubmed]
  26. Binding of host collectins to the pathogenic yeast Cryptococcus neoformans: human surfactant protein D acts as an agglutinin for acapsular yeast cells. Schelenz, S., Malhotra, R., Sim, R.B., Holmskov, U., Bancroft, G.J. Infect. Immun. (1995) [Pubmed]
  27. Lung and salivary scavenger receptor glycoprotein-340 contribute to the host defense against influenza A viruses. Hartshorn, K.L., White, M.R., Mogues, T., Ligtenberg, T., Crouch, E., Holmskov, U. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  28. Contributions of the N- and C-terminal domains of surfactant protein d to the binding, aggregation, and phagocytic uptake of bacteria. Hartshorn, K.L., White, M.R., Crouch, E.C. Infect. Immun. (2002) [Pubmed]
  29. Surfactant proteins A and D: disease markers. Kuroki, Y., Takahashi, H., Chiba, H., Akino, T. Biochim. Biophys. Acta (1998) [Pubmed]
  30. Increased expression of surfactant protein A and D in rheumatoid arthritic synovial fluid (RASF). Kankavi, O. Croat. Med. J. (2006) [Pubmed]
  31. Expression and localization of lung surfactant protein A in human tissues. Madsen, J., Tornoe, I., Nielsen, O., Koch, C., Steinhilber, W., Holmskov, U. Am. J. Respir. Cell Mol. Biol. (2003) [Pubmed]
  32. Organization of the human SP-A and SP-D loci at 10q22-q23. Physical and radiation hybrid mapping reveal gene order and orientation. Hoover, R.R., Floros, J. Am. J. Respir. Cell Mol. Biol. (1998) [Pubmed]
  33. Surfactant protein A2 gene expression by human airway submucosal gland cells. Saitoh, H., Okayama, H., Shimura, S., Fushimi, T., Masuda, T., Shirato, K. Am. J. Respir. Cell Mol. Biol. (1998) [Pubmed]
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