Amelioration of habu venom-induced glomerular lesions: potential role for platelet secretory proteins

Abstract

Platelets have been implicated as mediators of mesangial cell proliferation. Of interest is a potential role for platelet secretory proteins (some of which are known to be growth factors) in proliferative glomerular disease. This study examines the effect of sulindac, an inhibitor of platelet thromboxane A2 generation and platelet activation, on the development of glomerular cystic and proliferative lesions after injection of habu snake venom (HSV). To examine the association of platelet secretory proteins with glomerular lesions after HSV, antiserum against a pool of platelet secretory cationic proteins (PSCPs) was used, by immunofluorescence, as a marker of the secretory component of platelet activation in platelet-compromised and normal rats. Uninephrectomized rats received sulindac (60 mg/kg body weight) or vehicle daily before and after HSV (2 mg/kg body weight, IV). Glomerular cysts, proliferative nodules, and mixed lesions (cystic plus proliferative) were quantitated and PSCP localization was examined 48 hours after HSV. Sulindac substantially reduced the total number of glomerular lesions and preferentially reduced proliferative lesions when compared with controls. PSCPs localized in glomerular lesions in both groups and paralleled the severity of disease, but overall intensity of PSCP staining was less in sulindac-treated rats. Sulindac did not alter renal function before HSV, ruling out hemodynamic factors. The concomitant localization of PSCPs in glomerular lesions and amelioration by antiplatelet therapy supports a role for platelet secretory proteins in this model of proliferative glomerular disease.