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

Departments of 1 Medicine and 2 Biochemistry, The Lawson Research Institute, St. Joseph's Health Center, The University of Western Ontario, London, Ontario, Canada N6A 4V2; 3 Department of Pulmonary and Critical Care Medicine, Children's Hospital Medical Center, Cincinnati 45229-3039; 4 Department of Pulmonary Biology, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0564; 5 Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, Alabama 35233; 6 Department of Cell Biology, Duke University, Durham, North Carolina 27710; and 7 Department of Biochemistry, Vanderbilt University School of Medicine, Veterans Affairs Medical Center, Nashville, Tennessee 37212-2637 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. surfactant-associated protein A; T lymphocyte; proliferation; suppression; receptor