Modulation by lipid mediators of immune complex-induced lung inflammation in mice

The present study characterized a murine model of immune complex-induced pn eumonitis and investigated the role of platelet-activating factor (PAF) and eicosanoids as mediators of lung neutrophil infiltration and hemorrhagic l esions. Rabbit antibodies to bovine serum albumin were injected into the ai rways and bovine serum albumin was injected intravenously into C3H/HePas an d BALB/c mice. After 24 h, a significant increase in neutrophil infiltratio n and hemoglobin concentration in the bronchoalveolar lavage fluid and lung parenchyma was observed in both strains despite the C3H/HePas strain being 10 times more sensitive to PAF. Neutrophil influx and vascular lesions wer e not affected by pre-treatment of the mice with the PAF receptor antagonis t, WEB 2170 (5-(2-chlorphenyl)carbonyl)3,4-dihydro-10-methyl-3-((4-morpholi nyl)-2H,7H-cyclopenta(4,5)thieno(3,2-f)(1,2,4)-triazolo0(4,3-a)(1,4)-diazep ine). In contrast, neutrophil influx and vascular lesions were increased by the cyclo-oxygenase inhibitor, indomethacin, and reduced by the inhibitor of leukotriene synthesis, MK 886 (3-[1-(4-chlorobenzyl-3-t-butyl-thio-t-iso propyl-indol-2y-1]-2-2-dimethylpropanoic acid) and by the leukotriene B-4 r eceptor antagonist, RO 0254094 (2-[(5-carboxypentyl)-6-[6-[3,4-dihidro-4-ox o-8-propyl-2H-1-benzopyran-7-yl)hexyl] benzenepropanoic acid). Increased le vels of leukotriene B-4, leukotriene C-4/D-4, thromboxane B-2 were found in bronchoalveolar lavage fluid 4 h after induction of the reaction. There is also a tendency to increased prostaglandins E-2 levels. Neutrophil infiltr ation and vascular lesions in immune complex-induced pneumonitis in mice ar e mediated by leukotriene B-4. (C) 1998 Elsevier Science B.V. All rights re served.