Platelet-activating factor (PAF) has been implicated as a potential mediator in renal immune injury, but little is known on the mechanisms by which this endogenous
phospholipid could contribute to the development of glomerular
proteinuria that occurs during immunologically mediated inflammatory reactions. Several experimental models of renal immune injury, including hyperacute kidney allograft rejection, acute
serum sickness and nephrotoxic
nephritis, and human studies have clearly indicated that renal damage is associated with increased intraglomerular formation of PAF. However, a definitive proof of its pathophysiologic role has been obtained only by pharmacological inhibition of PAF activity at receptor level. In this context we have documented that the PAF receptor antagonist
L-652,731 markedly prevented renal function deterioration and development of
proteinuria, and reduced glomerular hypercellularity,
fibrin deposition in Bowman's space, and tubular cast formation in a rabbit model of nephrotoxic serum
nephritis. Concerning the mechanisms by which PAF may induce
proteinuria, it has been suggested that PAF increases glomerular permeability to
proteins through the release of cationic
proteins from platelets and polymorphonuclear neutrophils infiltrating the glomerular tuft, and their deposition in the glomerular capillary wall with loss of fixed anionic charges. We have recently shown that in isolated rat kidney preparations perfused with a cell-free medium, the addition of PAF, but not its vehicle or 2-lyso-PAF, to the perfusate caused a progressive increase in urinary
protein excretion. PAF-induced
proteinuria was prevented by exposure of isolated kidneys to the PAF receptor antagonist L-652,731.(ABSTRACT TRUNCATED AT 250 WORDS)