SURFACTANT PROTEIN-A INHIBITS T-CELL PROLIFERATION VIA ITS COLLAGEN-LIKE TAIL AND A 210-KDA RECEPTOR

Investigation of possible mechanisms to describe the hyporesponsivenes s of pulmonary leukocytes has led to the study of pulmonary surfactant and its constituents as immune suppressive agents. Pulmonary surfacta nt is a phospholipid-protein mixture that reduces surface tension in t he lung and prevents collapse of the alveoli. The most abundant protei n in this mixture is a hydrophilic molecule termed surfactant-associat ed protein A (SP-A). Previously, we showed that bovine (b) SP-A can in hibit 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 inhibi ted human T lymphocyte proliferation in a dose-dependent manner. A str ucturally similar collagenous protein, Clq, did not block the in vitro inhibitory action of SP-A. The addition of large concentrations of ma nnan to SP-A-treated cultures also did not disrupt inhibition, suggest ing that the effect is not mediated by the carbohydrate recognition do main 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 dom ain was responsible for the inhibition of T cell proliferation. A poly clonal antiserum directed against an SP-A receptor (SP-RS10) completel y blocked the inhibition of T cell proliferation by SP-A. These result s emphasize a potential role for SP-A in dampening lymphocyte response s 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.