Platelet-complement interactions in mesangial proliferative nephritis in the rat

Abstract

Complement has been reported to mediate mesangiolysis and glomerular hypercellularity in the rat in a model of glomerulonephritis (GN) induced with anti-Thy 1 antibody. To investigate the mechanism for the complement-mediated hypercellularity, the authors first determined if the effect of complement depletion was to inhibit cell proliferation or whether the effect was primarily to inhibit leukocyte infiltration. Rats depleted of complement with cobra venom factor (CVF) had 1) significantly less mesangiolysis than controls at day 5 (0.6 +/- 0.1 versus 3.4 +/- 0.4, scale 0-4+, P less than 0.001); 2) less cell proliferation, as assessed by immunostaining for the proliferating cell nuclear antigen (PCNA)/cyclin, a cell-cycle-dependent antigen (0.5 +/- 0.1 versus 2.4 +/- 0.7 cells/glomerular cross-section, P less than 0.01); and 3) less leukocyte infiltration as assessed by immunohistochemical labeling (0.6 +/- 0.1 versus 1.9 +/- 0.3 cells/glomerular cross-section, P less than 0.01). Because it was reported recently that platelets also mediate glomerular cell proliferation in this model, this study examined whether the mechanism for complement-mediated cell proliferation involved an effect on glomerular platelet localization. The glomerular uptake of 111In-labeled platelets was quantitated in normal and CVF-treated rats at 1, 4, 12, and 24 hours after induction of GN. Rats with anti-Thy 1 GN had substantial glomerular accumulation of platelets at all times studied, peaking at 4 hours (608 +/- 171 platelets per glomerulus). Complement depletion profoundly reduced glomerular platelet localization in anti-Thy 1 GN (mean less than 35 platelets per glomerulus at all times studied, P less than 0.05). Thus these studies demonstrate an important role for complement in mediating platelet localization in anti-Thy 1 GN, an effect that may account for the complement-dependent, neutrophil-independent glomerular hypercellularity in this model.