Modulatory effect of arachidonate 5-lipoxygenation on glomerular cell proliferation in nephrotoxic serum nephritis

The modulatory effect of arachidonate 5-lipoxygenation on glomerular cell growth was assessed in rat nephrotoxic serum nephritis (NSN). After a single intravenous injection of anti-glomerular basement membrane immune serum, significant increments in glomerular proliferative activity (GPA)--assessed by tritiated thymidine incorporation in short-term glomerular cultures--occurred and were associated with enhanced glomerular cell proliferation, assessed in cortical sections by staining for the presence of proliferating cell nuclear antigen (PCNA) positive cells in glomeruli. Leukocyte depletion induced by x irradiation ameliorated the enhanced GPA and reduced PCNA (+) cell counts. The same effect was observed after treatment of rats with the arachidonate 5-lipoxygenase inhibitor MK886. These observations indicate that in NSN, leukocytes infiltrating glomeruli, and leukocyte-derived arachidonate 5-lipoxygenation eicosanoids promote glomerular cell proliferation.