Surfactant protein A inhibits T cell proliferation via its collagen- like tail and a 210-kDa receptor

Paul Borron, Francis X. Mccormack, Baher M. Elhalwagi, Zissis C. Chroneos, James F. Lewis, Sha Zhu, J. O. Rae Wright, Virginia L. Shepherd, Fred Possmayer, Kevin Inchley, Laurence J. Fraher

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Abstract

Investigation of possible mechanisms to describe the hyporesponsiveness of pulmonary leukocytes has led to the study of pulmonary surfactant and its constituents as immune suppressive agents. Pulmonary surfactant is a phospholipid-protein mixture that reduces surface tension in the lung and prevents collapse of the alveoli. The most abundant protein in this mixture is a hydrophilic molecule termed surfactant-associated protein A (SP-A). Previously, we showed that bovine (b) SP-A can inhibit human T lymphocyte proliferation and interleukin-2 production in vitro. Results presented in this investigation showed that different sources of human SP-A and bSP-A as well as recombinant rat SP-A inhibited human T lymphocyte proliferation in a dose-dependent manner. A structurally similar collagenous protein, C1q, did not block the in vitro inhibitory action of SP-A. The addition of large concentrations of mannan to SP-A-treated cultures also did not disrupt inhibition, suggesting that the effect is not mediated by the carbohydrate recognition domain of SP-A. Use of recombinant mutant SP-As revealed that a 36-amino acid Arg-Gly-Asp (RGD) motif-containing span of the collagen-like domain was responsible for the inhibition of T cell proliferation. A polyclonal antiserum directed against an SP-A receptor (SP-R210) completely blocked the inhibition of T cell proliferation by SP-A. These results emphasize a potential role for SP-A in dampening lymphocyte responses to exogenous stimuli. The data also provide further support for the concept that SP-A maintains a balance between the clearance of inhaled pathogens and protection against collateral immune-mediated damage.

Original languageEnglish (US)
Pages (from-to)L679-L686
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume275
Issue number4 19-4
StatePublished - Nov 9 1998

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Borron, P., Mccormack, F. X., Elhalwagi, B. M., Chroneos, Z. C., Lewis, J. F., Zhu, S., Rae Wright, J. O., Shepherd, V. L., Possmayer, F., Inchley, K., & Fraher, L. J. (1998). Surfactant protein A inhibits T cell proliferation via its collagen- like tail and a 210-kDa receptor. American Journal of Physiology - Lung Cellular and Molecular Physiology, 275(4 19-4), L679-L686.