Infiltration of glomerular mesangium by monocytes/macrophages is a prominent pathologic finding in many forms of glomerulonephritis (GN). While the mechanism(s) by which infiltration occurs is incompletely understood, monocyte adhesion to glomerular endothelial cells, provoked by inflammatory mediators, appears to be an important early step. In the present study, we assessed the influence of chemotactic peptides (C5a) and lipids (LTB4 and PAF) on adhesion of human monocytes and mesangial cells, to determine if mesangial cells (glomerular pericytes with smooth muscle properties) represent potential targets for adhesion of chemoattractant-activated monocytes following their diapedesis from the intravascular space. C5a and LTB4 provoked rapid (onset <1 min) monocyte-mesangial cell adhesion at nanomolar concentrations via actions with monocytes, while PAF was less potent in this regard. Monoclonal antibodies (mAb) were used to define the monocyte and mesangial cell adhesion molecules involved in these interactions. C5a- and LTB4-induced monocyte adhesion was inhibited (∼54%) by mAb against the common beta CD18 subunit of CD11/CD18 leukocyte integrins, while mAb against monocyte L-selectin was without effect. MAb against unique CD11 subunits were used to determine the relative contributions of different CD11/ CD18 integrins. In this regard, adhesion was inhibited by mAb against CD11b (∼41%), and CD11c (∼23%), but not CD11a. MAb against mesangial cell ICAM-1 afforded ∼27% reduction in adhesion, while mAb against VCAM-1, E-selectin, and P-selectin were without effect. GM-CSF, a cytokine generated by monocytes and mesangial cells, also provoked CD11/CD18-dependent adhesion, and primed monocytes to the actions of chemoattractants. Furthermore, priming of monocytes with GM-CSF appeared to promote mesangial cell injury during subsequent monocyte-mesangial cell coincubations. The adhesion-promoting actions of chemoattractants with monocytes were additive with those of cytokines with mesangial cells (that is, TNF-induced ICAM-1 and VCAM-1 expression). These data indicate that mesangial cells support adhesion of monocytes in vitro, and that chemotactic peptides and lipids act in concert with cytokines to promote adhesion and mesangial cell injury. Mesangial cells may be targets for monocyte adhesion in vivo and regulate monocyte trafficking during glomerular inflammation.
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