Glomerular localization of platelet secretory proteins in mesangial proliferative lesions induced by Habu snake venom

Platelets have been implicated in mesangial cell proliferation in experimental and clinical glomerular disease. In this study, the temporal relationship between release of platelet secretory cationic proteins (PSCP) and progression of mesangial hyperplasia was examined in a model of mesangial proliferative glomerulonephritis induced by Habu snake venom (HSV). Intravenous injection of HSV (2 mg/kg body wt) led to capillary dilatation and ballooning into cysts filled with prominent platelet aggregates at 8 hr and 24 hr. At 48 hr, lesions were heterogeneous, some exclusively cystic, others exclusively nodular (comprised of confluent proliferative mesangial cells). Most lesions were mixed, showing features of cystic lesions containing clusters of proliferating cells. At 72 hr, all lesions were exclusively nodular. These lesions were associated with persistent localization of PSCP, as demonstrated by immunofluorescence microscopy. At 8 hr, PSCP were restricted primarily to platelets, became more intensified and diffuse at later time intervals, and by 72 hr was demonstrated in a homogeneous pattern interspaced throughout the nodular lesions. Studies utilizing antiserum to a specific platelet secretory protein, platelet factor 4 (PF4), showed an identical pattern of glomerular localization. Thus, before and during the proliferative phase of nodular formation, mesangial cells are exposed to a milieu replete with PSCP, some of which are presumably biologically active, suggesting a potential role for platelet-secreted proteins in mesangial hyperplasia in this model.