Lung injury caused by cobra venom factor is reduced in rats raised on an essential fatty acid-deficient diet.
Arachidonate metabolites appear to be involved in lung injury caused by cobra venom factor (CVF)-induced complement and polymorphonuclear leukocyte (PMN) activation. These studies were designed to assess the effects of a dietary-induced deficiency of arachidonic acid on CVF-induced lung injury. Rats raised on an essential fatty acid-deficient (EFAD) diet exhibited the expected changes in fatty acid composition including decreased plasma levels of arachidonic acid and increased levels of 5,8,11-eicosatrienoic acid. In intact rats raised on the EFAD diet, CVF-induced lung injury was attenuated. When blood and excised lungs from rats raised on the normal diet were used, CVF caused pulmonary vascular constriction and acute lung injury, as evidenced by increased 125I-labeled bovine serum albumin accumulation in lung parenchyma and alveolar lavage fluid. The CVF-induced pulmonary artery pressor response and lung injury were reduced when blood perfusate or blood perfusate and excised lungs were obtained from rats raised on the EFAD diet. The pulmonary vascular constriction and lung injury were not attenuated when the blood perfusate was obtained from rats raised on the normal diet, irrespective of whether the excised lungs were obtained from rats raised on the normal or EFAD diet. PMNs obtained from rats raised on the EFAD diet demonstrated decreased superoxide production as well as impaired random migration and chemotaxis in vitro. In contrast, beta-glucuronidase release was quantitatively similar to PMNs from control rats. These data indicate that the EFAD diet-induced attenuation of CVF-induced pulmonary hypertension and acute lung injury is due to defective effector cells in blood rather than modified pulmonary target tissue.
Morganroth
M L
ML
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109.
Schoeneich
S O
SO
Till
G O
GO
Pickett
W
W
Ward
P A
PA
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D004546:Elapid Venoms / Q000633:toxicity*; D005228:Fatty Acids, Essential / Q000172:deficiency*; D005231:Fatty Acids, Unsaturated / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D012016:Reference Values; D014661:Vasoconstriction / Q000187:drug effects
D001095:Arachidonic Acids; D004546:Elapid Venoms; D005228:Fatty Acids, Essential; D005231:Fatty Acids, Unsaturated; C016310:cobra venom factor