Skip to main content
Archives of Disease in Childhood logoLink to Archives of Disease in Childhood
. 2003 Nov;88(11):981–984. doi: 10.1136/adc.88.11.981

The potential of recombinant surfactant protein D therapy to reduce inflammation in neonatal chronic lung disease, cystic fibrosis, and emphysema

H Clark 1, K Reid 1
PMCID: PMC1719357  PMID: 14612363

Full Text

The Full Text of this article is available as a PDF (167.6 KB).

Figure 1 .

Figure 1

The human collectins. Monomeric forms of SP-A and SP-D trimerise and associate into higher order oligomers.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnon S., Grigg J., Silverman M. Pulmonary inflammatory cells in ventilated preterm infants: effect of surfactant treatment. Arch Dis Child. 1993 Jul;69(1 Spec No):44–48. doi: 10.1136/adc.69.1_spec_no.44. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bals R., Weiner D. J., Wilson J. M. The innate immune system in cystic fibrosis lung disease. J Clin Invest. 1999 Feb;103(3):303–307. doi: 10.1172/JCI6277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Borron P. J., Crouch E. C., Lewis J. F., Wright J. R., Possmayer F., Fraher L. J. Recombinant rat surfactant-associated protein D inhibits human T lymphocyte proliferation and IL-2 production. J Immunol. 1998 Nov 1;161(9):4599–4603. [PubMed] [Google Scholar]
  4. Botas C., Poulain F., Akiyama J., Brown C., Allen L., Goerke J., Clements J., Carlson E., Gillespie A. M., Epstein C. Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D. Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11869–11874. doi: 10.1073/pnas.95.20.11869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bridges J. P., Davis H. W., Damodarasamy M., Kuroki Y., Howles G., Hui D. Y., McCormack F. X. Pulmonary surfactant proteins A and D are potent endogenous inhibitors of lipid peroxidation and oxidative cellular injury. J Biol Chem. 2000 Dec 8;275(49):38848–38855. doi: 10.1074/jbc.M005322200. [DOI] [PubMed] [Google Scholar]
  6. Clark H. W., Reid K. B., Sim R. B. Collectins and innate immunity in the lung. Microbes Infect. 2000 Mar;2(3):273–278. doi: 10.1016/s1286-4579(00)00301-4. [DOI] [PubMed] [Google Scholar]
  7. Clark Howard, Palaniyar Nades, Strong Peter, Edmondson Jess, Hawgood Samuel, Reid Kenneth B. M. Surfactant protein D reduces alveolar macrophage apoptosis in vivo. J Immunol. 2002 Sep 15;169(6):2892–2899. doi: 10.4049/jimmunol.169.6.2892. [DOI] [PubMed] [Google Scholar]
  8. Clark Howard, Reid Kenneth B. M. Structural requirements for SP-D function in vitro and in vivo: therapeutic potential of recombinant SP-D. Immunobiology. 2002 Sep;205(4-5):619–631. doi: 10.1078/0171-2985-00159. [DOI] [PubMed] [Google Scholar]
  9. Clement A., Chadelat K., Sardet A., Grimfeld A., Tournier G. Alveolar macrophage status in bronchopulmonary dysplasia. Pediatr Res. 1988 May;23(5):470–473. doi: 10.1203/00006450-198805000-00007. [DOI] [PubMed] [Google Scholar]
  10. Crouch E. C., Persson A., Griffin G. L., Chang D., Senior R. M. Interactions of pulmonary surfactant protein D (SP-D) with human blood leukocytes. Am J Respir Cell Mol Biol. 1995 Apr;12(4):410–415. doi: 10.1165/ajrcmb.12.4.7695920. [DOI] [PubMed] [Google Scholar]
  11. D'Agostini F., Balansky R. M., Izzotti A., Lubet R. A., Kelloff G. J., De Flora S. Modulation of apoptosis by cigarette smoke and cancer chemopreventive agents in the respiratory tract of rats. Carcinogenesis. 2001 Mar;22(3):375–380. doi: 10.1093/carcin/22.3.375. [DOI] [PubMed] [Google Scholar]
  12. Fadok V. A., Bratton D. L., Guthrie L., Henson P. M. Differential effects of apoptotic versus lysed cells on macrophage production of cytokines: role of proteases. J Immunol. 2001 Jun 1;166(11):6847–6854. doi: 10.4049/jimmunol.166.11.6847. [DOI] [PubMed] [Google Scholar]
  13. Fadok V. A., Bratton D. L., Henson P. M. Phagocyte receptors for apoptotic cells: recognition, uptake, and consequences. J Clin Invest. 2001 Oct;108(7):957–962. doi: 10.1172/JCI14122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fearon D. T., Locksley R. M. The instructive role of innate immunity in the acquired immune response. Science. 1996 Apr 5;272(5258):50–53. doi: 10.1126/science.272.5258.50. [DOI] [PubMed] [Google Scholar]
  15. Greene K. E., King T. E., Jr, Kuroki Y., Bucher-Bartelson B., Hunninghake G. W., Newman L. S., Nagae H., Mason R. J. Serum surfactant proteins-A and -D as biomarkers in idiopathic pulmonary fibrosis. Eur Respir J. 2002 Mar;19(3):439–446. doi: 10.1183/09031936.02.00081102. [DOI] [PubMed] [Google Scholar]
  16. Grigg J. M., Savill J. S., Sarraf C., Haslett C., Silverman M. Neutrophil apoptosis and clearance from neonatal lungs. Lancet. 1991 Sep 21;338(8769):720–722. doi: 10.1016/0140-6736(91)91443-x. [DOI] [PubMed] [Google Scholar]
  17. Guo X., Lin H. M., Lin Z., Montaño M., Sansores R., Wang G., DiAngelo S., Pardo A., Selman M., Floros J. Surfactant protein gene A, B, and D marker alleles in chronic obstructive pulmonary disease of a Mexican population. Eur Respir J. 2001 Sep;18(3):482–490. doi: 10.1183/09031936.01.00043401. [DOI] [PubMed] [Google Scholar]
  18. Hargitai B., Szabó V., Hajdú J., Harmath A, Pataki M., Farid P., Papp Z., Szende B. Apoptosis in various organs of preterm infants: histopathologic study of lung, kidney, liver, and brain of ventilated infants. Pediatr Res. 2001 Jul;50(1):110–114. doi: 10.1203/00006450-200107000-00020. [DOI] [PubMed] [Google Scholar]
  19. Hickling T. P., Bright H., Wing K., Gower D., Martin S. L., Sim R. B., Malhotra R. A recombinant trimeric surfactant protein D carbohydrate recognition domain inhibits respiratory syncytial virus infection in vitro and in vivo. Eur J Immunol. 1999 Nov;29(11):3478–3484. doi: 10.1002/(SICI)1521-4141(199911)29:11<3478::AID-IMMU3478>3.0.CO;2-W. [DOI] [PubMed] [Google Scholar]
  20. Honda Y., Takahashi H., Kuroki Y., Akino T., Abe S. Decreased contents of surfactant proteins A and D in BAL fluids of healthy smokers. Chest. 1996 Apr;109(4):1006–1009. doi: 10.1378/chest.109.4.1006. [DOI] [PubMed] [Google Scholar]
  21. Kuan S. F., Rust K., Crouch E. Interactions of surfactant protein D with bacterial lipopolysaccharides. Surfactant protein D is an Escherichia coli-binding protein in bronchoalveolar lavage. J Clin Invest. 1992 Jul;90(1):97–106. doi: 10.1172/JCI115861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. LeVine A. M., Whitsett J. A., Gwozdz J. A., Richardson T. R., Fisher J. H., Burhans M. S., Korfhagen T. R. Distinct effects of surfactant protein A or D deficiency during bacterial infection on the lung. J Immunol. 2000 Oct 1;165(7):3934–3940. doi: 10.4049/jimmunol.165.7.3934. [DOI] [PubMed] [Google Scholar]
  23. LeVine A. M., Whitsett J. A. Pulmonary collectins and innate host defense of the lung. Microbes Infect. 2001 Feb;3(2):161–166. doi: 10.1016/s1286-4579(00)01363-0. [DOI] [PubMed] [Google Scholar]
  24. Li Ying-Hua, Tullus Kjell. Microbial infection and inflammation in the development of chronic lung disease of prematurity. Microbes Infect. 2002 Jun;4(7):723–732. doi: 10.1016/s1286-4579(02)01595-2. [DOI] [PubMed] [Google Scholar]
  25. Madan T., Eggleton P., Kishore U., Strong P., Aggrawal S. S., Sarma P. U., Reid K. B. Binding of pulmonary surfactant proteins A and D to Aspergillus fumigatus conidia enhances phagocytosis and killing by human neutrophils and alveolar macrophages. Infect Immun. 1997 Aug;65(8):3171–3179. doi: 10.1128/iai.65.8.3171-3179.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Madan T., Kishore U., Singh M., Strong P., Clark H., Hussain E. M., Reid K. B., Sarma P. U. Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens. J Clin Invest. 2001 Feb;107(4):467–475. doi: 10.1172/JCI10124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Majo J., Ghezzo H., Cosio M. G. Lymphocyte population and apoptosis in the lungs of smokers and their relation to emphysema. Eur Respir J. 2001 May;17(5):946–953. doi: 10.1183/09031936.01.17509460. [DOI] [PubMed] [Google Scholar]
  28. Mariencheck W., Crouch E. Modulation of surfactant protein D expression by glucocorticoids in fetal rat lung. Am J Respir Cell Mol Biol. 1994 Apr;10(4):419–429. doi: 10.1165/ajrcmb.10.4.8136157. [DOI] [PubMed] [Google Scholar]
  29. Merritt T. A., Stuard I. D., Puccia J., Wood B., Edwards D. K., Finkelstein J., Shapiro D. L. Newborn tracheal aspirate cytology: classification during respiratory distress syndrome and bronchopulmonary dysplasia. J Pediatr. 1981 Jun;98(6):949–956. doi: 10.1016/s0022-3476(81)80603-8. [DOI] [PubMed] [Google Scholar]
  30. Miyamura K., Malhotra R., Hoppe H. J., Reid K. B., Phizackerley P. J., Macpherson P., López Bernal A. Surfactant proteins A (SP-A) and D (SP-D): levels in human amniotic fluid and localization in the fetal membranes. Biochim Biophys Acta. 1994 Jan 20;1210(3):303–307. doi: 10.1016/0005-2760(94)90233-x. [DOI] [PubMed] [Google Scholar]
  31. Nogee L. M., Garnier G., Dietz H. C., Singer L., Murphy A. M., deMello D. E., Colten H. R. A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds. J Clin Invest. 1994 Apr;93(4):1860–1863. doi: 10.1172/JCI117173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. O'Riordan D. M., Standing J. E., Kwon K. Y., Chang D., Crouch E. C., Limper A. H. Surfactant protein D interacts with Pneumocystis carinii and mediates organism adherence to alveolar macrophages. J Clin Invest. 1995 Jun;95(6):2699–2710. doi: 10.1172/JCI117972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ofek I., Mesika A., Kalina M., Keisari Y., Podschun R., Sahly H., Chang D., McGregor D., Crouch E. Surfactant protein D enhances phagocytosis and killing of unencapsulated phase variants of Klebsiella pneumoniae. Infect Immun. 2001 Jan;69(1):24–33. doi: 10.1128/IAI.69.1.24-33.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Postle A. D., Mander A., Reid K. B., Wang J. Y., Wright S. M., Moustaki M., Warner J. O. Deficient hydrophilic lung surfactant proteins A and D with normal surfactant phospholipid molecular species in cystic fibrosis. Am J Respir Cell Mol Biol. 1999 Jan;20(1):90–98. doi: 10.1165/ajrcmb.20.1.3253. [DOI] [PubMed] [Google Scholar]
  35. Rauprich P., Möller O., Walter G., Herting E., Robertson B. Influence of modified natural or synthetic surfactant preparations on growth of bacteria causing infections in the neonatal period. Clin Diagn Lab Immunol. 2000 Sep;7(5):817–822. doi: 10.1128/cdli.7.5.817-822.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sandford Andrew J., Joos Ladina, Paré Peter D. Genetic risk factors for chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2002 Mar;8(2):87–94. doi: 10.1097/00063198-200203000-00002. [DOI] [PubMed] [Google Scholar]
  37. Savill J. Apoptosis in resolution of inflammation. J Leukoc Biol. 1997 Apr;61(4):375–380. doi: 10.1002/jlb.61.4.375. [DOI] [PubMed] [Google Scholar]
  38. Schelenz S., Malhotra R., Sim R. B., Holmskov U., Bancroft G. J. Binding of host collectins to the pathogenic yeast Cryptococcus neoformans: human surfactant protein D acts as an agglutinin for acapsular yeast cells. Infect Immun. 1995 Sep;63(9):3360–3366. doi: 10.1128/iai.63.9.3360-3366.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Speer C. P. Inflammatory mechanisms in neonatal chronic lung disease. Eur J Pediatr. 1999 Dec;158 (Suppl 1):S18–S22. doi: 10.1007/pl00014314. [DOI] [PubMed] [Google Scholar]
  40. Strong P., Kishore U., Morgan C., Lopez Bernal A., Singh M., Reid K. B. A novel method of purifying lung surfactant proteins A and D from the lung lavage of alveolar proteinosis patients and from pooled amniotic fluid. J Immunol Methods. 1998 Nov 1;220(1-2):139–149. doi: 10.1016/s0022-1759(98)00160-4. [DOI] [PubMed] [Google Scholar]
  41. Strong P., Reid K. B. M., Clark H. Intranasal delivery of a truncated recombinant human SP-D is effective at down-regulating allergic hypersensitivity in mice sensitized to allergens of Aspergillus fumigatus. Clin Exp Immunol. 2002 Oct;130(1):19–24. doi: 10.1046/j.1365-2249.2002.01968.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Vandivier R. William, Fadok Valerie A., Ogden Carol Anne, Hoffmann Peter R., Brain Joseph D., Accurso Frank J., Fisher James H., Greene Kelly E., Henson Peter M. Impaired clearance of apoptotic cells from cystic fibrosis airways. Chest. 2002 Mar;121(3 Suppl):89S–89S. doi: 10.1378/chest.121.3_suppl.89s. [DOI] [PubMed] [Google Scholar]
  43. Wang J. Y., Shieh C. C., You P. F., Lei H. Y., Reid K. B. Inhibitory effect of pulmonary surfactant proteins A and D on allergen-induced lymphocyte proliferation and histamine release in children with asthma. Am J Respir Crit Care Med. 1998 Aug;158(2):510–518. doi: 10.1164/ajrccm.158.2.9709111. [DOI] [PubMed] [Google Scholar]
  44. Wang J. Y., Yeh T. F., Lin Y. C., Miyamura K., Holmskov U., Reid K. B. Measurement of pulmonary status and surfactant protein levels during dexamethasone treatment of neonatal respiratory distress syndrome. Thorax. 1996 Sep;51(9):907–913. doi: 10.1136/thx.51.9.907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wert S. E., Yoshida M., LeVine A. M., Ikegami M., Jones T., Ross G. F., Fisher J. H., Korfhagen T. R., Whitsett J. A. Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice. Proc Natl Acad Sci U S A. 2000 May 23;97(11):5972–5977. doi: 10.1073/pnas.100448997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. van Rozendaal B. A., van de Lest C. H., van Eijk M., van Golde L. M., Voorhout W. F., van Helden H. P., Haagsman H. P. Aerosolized endotoxin is immediately bound by pulmonary surfactant protein D in vivo. Biochim Biophys Acta. 1999 Aug 30;1454(3):261–269. doi: 10.1016/s0925-4439(99)00042-3. [DOI] [PubMed] [Google Scholar]
  47. von Bredow C., Birrer P., Griese M. Surfactant protein A and other bronchoalveolar lavage fluid proteins are altered in cystic fibrosis. Eur Respir J. 2001 Apr;17(4):716–722. doi: 10.1183/09031936.01.17407160. [DOI] [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood are provided here courtesy of BMJ Publishing Group

RESOURCES