Inflammation and tissue destruction in periodontal diseases are thought to be the result of a number of pathologic processes. Activation of the complement system is thought to occur in the periodontal tissues, but the mechanisms linking complement activation and disease pathogenesis are unclear. Metabolites of arachidonic acid (AA) including prostaglandins (PG's) and thromboxanes, are present in elevated concentrations in inflammed periodontal tissues, and may account for some of the pathologic processes which occur. We have recently shown that C3 cleavage products C3b and C3bi stimulate PG release by human monocytes.
One aim of the proposed studies will be to expand upon this observation by determining whether this phenomemon affects PG-sensitive biologic functions of lymphoid cells, including lymphokine production, complement component synthesis, and immunoglobulin production. A second objective will be to analyze the effect of C3 fragments and immune complexes on AA metabolism by human neutrophils. Such analyses will include determination of specificity of C3 fragments, dose-response and kinetic criteria, and the differentiation of the effects of particle-bound and soluble fragments. In addition, analysis of phospholipid turnover in cell membranes resulting from interaction of C3b and its fragments with membrane complement receptors will be accomplished. A further objective is to more completely define the AA metabolites that result following stimulation with C3b, C3bi, and immune complexes by analysis utilizing thin-layer chromatography and high pressure liquid chromatography.
