MODULATORY EFFECT OF ARACHIDONATE 5-LIPOXYGENATION ON GLOMERULAR CELL-PROLIFERATION IN NEPHROTOXIC SERUM NEPHRITIS

The modulatory effect of arachidonate 5-lipoxygenation on glomerular c ell growth was assessed in rat nephrotoxic serum nephritis (NSN). Afte r a single intravenous injection of anti-glomerular basement membrane immune serum, significant increments in glomerular proliferative activ ity (GPA)-assessed by tritiated thymidine incorporation in short-term glomerular cultures-occurred and were associated with enhanced glomeru lar cell proliferation, assessed in cortical sections by staining for the presence of proliferating cell nuclear antigen (PCNA) positive cel ls in glomeruli. Leukocyte depletion induced by x irradiation ameliora ted the enhanced GPA and reduced PCNA (+) cell counts. The same effect was observed after treatment of rats with the arachidonate 5-lipoxyge nase inhibitor MK886. These observations indicate that in NSN, leukocy tes infiltrating glomeruli, and leukocyte-derived arachidonate 5-lipox ygenation eicosanoids promote glomerular cell proliferation.