Platelet-activating factor-induced loss of glomerular anionic charges.

The urinary protein excretion rate, the glomerular localization of cationic proteins (CP) derived from platelets and polymorphonuclear neutrophils (PMN) and the loss of fixed anionic charges were studied in rabbits infused with synthetic 1-0-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine [platelet activating factor (PAF), 1.5 micrograms/kg in 2 ml of saline containing 0.25% bovine serum albumin (BSA)]. The urinary protein excretion rate, unaffected by diphenhydramine, an antihistaminic agent, reached its maximum at 180 min and decreased 24 hr after PAF infusion. The localization of CP derived from platelets and PMN was investigated by immunofluorescence using specific antisera. Platelet-derived CP were detectable in glomeruli at 15 min and, particularly, at 180 min after PAF infusion. Cells positive for CP derived from PMN accumulated within 15 min in the glomerular capillaries and, later (180 min), cytoplasmic depletion and localization in glomerular capillary walls occurred. CP deposits were associated with the loss of fixed anionic charges as detected by ruthenium red and colloidal iron staining. Rabbits infused with 1-0-octadecyl-sn-glyceryl-3-phosphorylcholine (lyso-PAF) or saline-BSA alone had none of the alterations described above. The development of proteinuria, the glomerular localization of platelet- and PMN-derived CP and the concomitant loss of fixed anionic charges suggested the possibility that, once CP were released in the circulation from PAF-stimulated platelets and PMN, they bound to, and neutralized, fixed anionic charges, resulting in enhanced glomerular permeability.