Functional heterogeneity of human rheumatoid synovial tissue macrophages

Neovascularization plays an important role in the formation of the rheumatoid (RA) synovial pannus. A subpopulation of RA macrophages (F₃) (density 1.042-1.062 g/ml) has been shown to induce neovascularization in an in vivo rat corneal model of angiogenesis. We have found that conditioned medium from F₃ macrophages induced significantly more endothelial migration (p<0.001) and mononuclear cell factor activity (p<0.001) than did conditioned medium from F₂ macrophages (density 0.998-1.042 g/ml). Exposure of these macrophages to lipopolysaccharide did not increase production of these activities. RA synovial tissue macrophages appear to be (1) heterogeneous in their production, and (2) maximally activated for expression of these activities in vivo. F₃ macrophages may be important in mediating both the fibroproliferative and destructive phases of RA.