title: Role of platelet-activating factor in renal immune injury and proteinuria.
abstract: 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)
authors: Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
authors: N
authors: N
authors: Perico
authors: G
authors: G
authors: Remuzzi
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001323:Autoantibodies; D005919:Glomerular Filtration Rate / Q000502:physiology; D005921:Glomerulonephritis / Q000209:etiology*; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology; D010972:Platelet Activating Factor / Q000502:physiology*; D011507:Proteinuria / Q000209:etiology*
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D010972:Platelet Activating Factor; C051951:antiglomerular basement membrane antibody