The intent of this study was to visualize changes in the density and location of fibrinogen-related antigen (FRA) depositions within the murine vitreous space during the formation of a chronic mycobacterial-induced uveitis (CMIU) granuloma. Concurrent changes in cellular morphology of the granuloma were also examined. Fibrinogen derivatives within the exudates of granulomatous cell-mediated inflammations may induce physical induration and numerous other phlogistic effects. However, technical limitations of conventional FRA staining methods have tended to underestimate the extent of their presence within this category of inflammatory lesions. Conventional H and E sections of the CMIU granuloma confirmed the classic progression-early PMN influx, monocyte maturation and final macrophage and epithelioid cell dominance-described for such lesions. Avidin-biotin-complex staining utilizing a polyclonal mouse antifibrinogen then revealed a progressive increase in amorphous extracellular fibrinogen-FRA-positive staining material as the granuloma evolved. Thus, on day one the PMN influx showed no evidence of fibrinogen-FRA staining; at one week heavy staining was evident in the anterior chamber and in consolidated (i.e. macrophage) regions of the granuloma; at one month a heavy uniform staining appeared throughout the indurated granuloma where macrophages and epithelioid cells predominated. Patterns of heavy deposition on macrophage surfaces were suggested. The likelihood that bulky accumulations of FRA in mature granulomas are not solely fibrin, and may account for granulomatous induration and persistence, is discussed.
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