Characterization of platelet-derived growth factor β-receptor expressing cells in the vasculature of human rheumatoid synovium

Platelet-derived growth factor (PDGF) β-receptor expression in normal and rheumatoid synovia was investigated by double immunofluorescence staining of frozen sections and by in situ hybridization. In the inflamed synovia, PDGF β-receptor mRNA was present in vascular cells, as well as in discrete stromal cells. PDGF β-receptor expressing cells in rheumatoid synovia were characterized by double immunofluorescence staining using the PDGFR-B2 monoclonal antibody at a concentration at which this antibody merely stained granular accumulations of PDGF β-receptors. Granular accumulations of PDGF β-receptors were articulate in blood vessel cells, but also appeared in discrete stromal cells. Thus, the overall distribution of cells having granular accumulations of PDGF β-receptors was similar to the distribution of cells expressing PDGF β-receptor mRNA. Double immunofluorescence stainings showed that: (a) a majority (>90%) of resident macrophages did not express granular PDGF β-receptor staining, but macrophages were often juxtaposed to PDGF β-receptor-positive cells; (b) T lymphocytes did not express PDGF β-receptors, but these cells were frequently found in the proximity of cells stained by PDGFR-B2; (c) in some blood vessels both HLA-DR expressing cells and PDGF β-receptor expressing cells could be visualized, whereas in other blood vessels, cells expressing only one of these activation markers could be detected; (d) smooth muscle cells in blood vessels contained PDGF β-receptors; and (e) capillary endothelial cells in the inflamed synovia recurrently displayed granular PDGF β-receptor staining. The granular accumulations of PDGF β-receptors may reflect internalization of the receptor as a result of paracrine or autocrine ligand stimulation. In support of such a possibility are the findings that elevated levels of PDGF B chain mRNA were detected by in situ hybridization in the inflamed synovia, and that cells expressing PDGF B chain mRNA were distributed similarly to cells expressing PDGF β-receptor mRNA. Taken together, the results indicate that PDGF has a role in the inflammatory process in rheumatoid synovitis, most likely by stimulating proliferative events in the vasculature.