SEQUENTIAL EXPRESSION OF CELLULAR FIBRONECTIN BY PLATELETS, MACROPHAGES, AND MESANGIAL CELLS IN PROLIFERATIVE GLOMERULONEPHRITIS

Fibronectin (Fn) regulates cell migration, proliferation, and extracel lular matrix formation during embryogenesis, angiogenesis, and wound h ealing. Fn also promotes mesangial cell migration and proliferation in vitro and contributes to extracellular matrix formation and tissue re modeling during glomerular disease. In this study, we examined, by imm unohistochemistry and in situ hybridization, the temporal glomerular l ocalization and cellular sources of Fn in Habu snake venom (HSV)-induc ed proliferative glomerulonephritis. Early HSV-induced glomerular lesi ons consisted of microaneurysms devoid of resident glomerular cells an d filled with platelets, leukocytes, and erythrocytes. Over the course of the disease, mesangial cells migrated into the lesions, proliferat ed, and formed a confluent cellular mass. Fn was present in lesions be ginning at 8 hours, with highest intensity at 72 hours and diminishing at 2 weeks after HSV. Staining for Fn at 8 and 24 hours after HSV was attributed to platelets and macrophages. In situ hybridization and ph enotypic identification of cell types within lesions revealed macropha ges as the predominant source of cellular Fn mRNA at these times. At 4 8 hours after HSV, Fn mRNA was expressed in proliferating mesangial ce lls in addition to macrophages. Most cells in lesions at 72 hours afte r HSV were mesangial, at a time when expression of Fn mRNA peaked. Cel lular expression for Fn mRNA and translated protein declined at 2 week s after HSV. These studies support the hypothesis that Fn, derived fro m platelets and macrophages, provides a provisional matrix involved wi th mesangial cell migration into glomerular lesions. Fn produced by me sangial cells might contribute to the formation of a stable extracellu lar matrix.