As part of a broader interest in the human platelet as a potential effector cell capable of participating in immunopathologic tissue injury and inflammation, this proposal focuses of membrane receptors potentially involved in platelet adhesion to and activation by immunologic reactants. Specifically targeted for study are platelet FcGamma receptors and putative complement receptors, i.e., platelet surface molecules responsive to certain particle-bound complement proteins. Particulate complexes formed by the interaction of human plasma proteins (principally IgG, complement and fibrinogen) with yeast-derived zymosan are employed as a model system to elucidate the human platelet's responsiveness to multivalent arrays of such protein ligands on a surface, as might be encountered in immunopathologic processes involving deposits of immunoglobulins, complement components and fibrinogen/fibrin in blood vessels, glomeruli or joint spaces. Major emphasis will be devoted to (a) clarification of the mechanism(s) by which C5,C6, and C7 contribute to the platelet-stimulating action of zymosan immune complexes, and (b) experiments testing whether such responses are mediated through a novel type of platelet complement receptor. Isolation and initial molecular characterization of both the FcGamma receptor and the putative complement receptor will be undertaken. Comparison of platelet FcGamma receptor molecules with candidate FcGamma receptor molecules previously isolated from the human monocytes is an additional point of interest. It is hoped that these studies will lead to a clearer understanding of the mechanisms by which platelets can bind to tissue-fixed immune complexes, as well as the mechanisms by which such immune complexes can stimulate platelets to aggregate and/or release vasoactive mediators at the sites of immunologically induced inflammation.
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| Rosenfeld, S I; Ryan, D H; Looney, R J et al. (1987) Human Fc gamma receptors: stable inter-donor variation in quantitative expression on platelets correlates with functional responses. J Immunol 138:2869-73 |
| Rosenfeld, S I; Looney, R J; Leddy, J P et al. (1985) Human platelet Fc receptor for immunoglobulin G. Identification as a 40,000-molecular-weight membrane protein shared by monocytes. J Clin Invest 76:2317-22 |
