Effects of colony-stimulating factors on proliferation and activation of synovial cells

Summary Joint synovium of patients with rheumatoid arthritis plays an important role in initiation and progress of joint diseases. Proliferation and activation of synovial cells, including macrophages, are modulated by various cytokines and arachidoic acid metabolites. Two kinds of cytokines; granulocyte/macrophage colony-stimulating factors (GM-CSF), and monocyte/macrophage colony-stimulating factor (M-CSF) induce the proliferation or activation of monocyte/macrophages, and their progenitor cells or other stromal cells in bone marrow. We investigated the effects of GM-CSF and M-CSF on synovial cells. GM-CSF stimulated the proliferation of synovial cells,and its effect was enhanced by the presence of indomethacin, like that of a potent stimulator of synovial cells, interleukin-1 (IL-1). But GM-CSF did not induce the production of IL-1. M-CSF neither stimulated the proliferation of synovial cells nor induced production of IL-1 by synovial cells. It was suggested that GM-CSF played some role in the proliferation of synovial cells of the joints.     

Sj?gren's syndrome and mixed connective tissue disease.

We investigated the clinical significance of the close association of Sj?gren's syndrome (SS) with mixed connective tissue disease (MCTD) by analyzing the clinical manifestations, sialographic findings and immunological parameters of MCTD and primary SS. The prevalence of sialectasia or SS in MCTD was significantly higher than in any other connective tissue diseases. The prevalence of Raynaud's phenomenon, swollen fingers, arthralgias, lymphadenopathy, sclerodactyly, muscle weakness, fever and erythema was significantly higher in MCTD than in primary SS. There were no significant differences between these manifestations in MCTD patients with sialectasia or SS, and those in MCTD patients without sialectasia or SS. Although the levels or prevalence of the erythrocyte sedimentation rate, CRP, antinuclear factor, anti-DNA antibody and anti-RNP antibody were significantly greater in MCTD than in primary SS, there were no significant differences in the levels or the prevalence of laboratory abnormalities between MCTD with sialectasia or SS, and MCTD without sialectasia or SS. Moreover, there was a strict dissociation between the occurrence of anti-RNP antibody and anti-SS-B antibody both in MCTD and primary SS. These results suggest that the association of secondary SS or sialectasia in MCTD, although more common than in other connective tissue diseases, is merely a consequence of MCTD and does not influence the clinical course of MCTD.     

C1q binding to human vascular smooth muscle cells mediates immune complex deposition and superoxide generation

Evidence was obtained for the binding of Clq to the membrane of cultured vascular smooth muscle cells derived from human umbilical cord veins. Clq was fixed to the cell membrane at 4°C, whereas it was ingested into the cytoplasm, as a cytoplasmic inclusion, when tested at 37°C. The addition of Clq in advance inhibited the subsequent binding of Clq. Neither fibronectin nor laminin was detected on the cell membrane. Aggregated IgG bound to vascular smooth muscle cells in the case of preincubation with Clq at 4°C, whereas aggregated IgG did not bind to the cells in the absence of Clq. The addition of Clq molecules to the cells in suspension enhanced Superoxide generation by vascular smooth muscle cells. There was no effect of Clq on Superoxide generation by the cells in monolayer. These results suggest that Clq binds on the membrane of vascular smooth muscle cells via its specific receptor that mediates immune complex binding to the cells and Superoxide generation. These properties elucidate the mechanisms by which circulating immune complexes deposit in the vascular wall, and subsequent degradation of tissue components surrounding vascular smooth muscle cells occurs through oxidative burst of the cells.