Mechanisms underlying the anti-inflammatory effects of essential fatty acid deficiency in experimental glomerulonephritis. Inhibited release of a monocyte chemoattractant by glomeruli.
Injection of nephrotoxic serum into rats results in glomerular inflammation and proteinuria. Rats placed on an essential fatty acid (EFA)-deficient diet are protected from the glomerular macrophage infiltration and the ensuing proteinuria. To account for this protection, we studied EFA-deficient rats to determine if there were defects in macrophage chemotaxis. We also investigated the possibility that EFA deficiency diminishes the production of a glomerular chemoattractant for monocytes. In microchemotaxis assays EFA-deficient macrophages migrated normally. EFA-deficient serum did not appear to contain a chemotactic inhibitor. Cultured glomeruli from control and control nephritic rats were found to elaborate a chemoattractant for monocytes. This chemoattractant activity was markedly enhanced after induction of nephritis, was heat stable, was not altered by inhibition of cyclooxygenase, lipoxygenase, or platelet-activating factor, and did not depend on C or the glomerular inflammatory cell infiltrate. EFA-deficient glomeruli harvested from animals receiving injections with nephrotoxic serum produced markedly less chemoattractant activity than glomeruli from control nephritic animals. Lipid extraction of nephritic glomeruli from control animals yielded chemoattractant activity in the organic phase. Extracts of EFA-deficient nephritic glomeruli had considerably less activity. We propose that EFA deficiency attenuates glomerular inflammation by inhibiting the ability of glomeruli to produce a specific lipid monocyte chemoattractant after exposure to a nephritic stimulus.
Rovin
B H
BH
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Lefkowith
J B
JB
Schreiner
G F
GF
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D000818:Animals; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015777:Eicosanoids / Q000502:physiology; D005228:Fatty Acids, Essential / Q000172:deficiency*; D005921:Glomerulonephritis / Q000276:immunology*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000276:immunology*; D010972:Platelet Activating Factor / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew
D002630:Chemotactic Factors; D015777:Eicosanoids; D005228:Fatty Acids, Essential; D010972:Platelet Activating Factor; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine