Immune-complex alveolitis in the rat: evidence for platelet activating factor and leukotrienes as mediators of the vascular lesions.
In the present study we investigated the involvement of lipid mediators in an experimental model of immune-complex alveolitis induced in rat lungs by intrabronchial instillation of rabbit antibodies to ovalbumin followed by i.v. injection of the antigen. It was found that the reaction did not induce detectable oedema, as measured by the dry:wet weight ratio. A marked influx of neutrophils was observed in the bronchoalveolar lavage fluid, progressing from 6 to 24 h in parallel with the development of haemorrhagic lesions in lung parenchyma. The intensity of these lesions, evaluated by the concentration of extravascular haemoglobin, was not significantly affected by pretreatment of the animals with a cyclo-oxygenase inhibitor (indomethacin), a thromboxane inhibitor (econazole) or a thromboxane antagonist (L-655,240). However, the antagonists of platelet activating factor (PAF), WEB-2086 and BN-52021, and the lipoxygenase inhibitors, nor-dihydroguaiaretic acid and L-663,536, all significantly inhibited the haemorrhagic lesions. A peptide leukotriene antagonist (L-660,711) had no effect. Furthermore, the PAF antagonists inhibited the levels of LTB4, but not of PGE2 and thromboxane, released into the bronchoalveolar space 1 h after induction of the reaction. These results suggest that the haemorrhagic lesions in this model of immune-complex alveolitis are mediated by PAF and leukotrienes, possibly LTB4.
de Lima
W T
WT
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, Brasil.
Sirois
P
P
Jancar
S
S
D000542:Alveolitis, Extrinsic Allergic / Q000503:physiopathology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D015232:Dinoprostone / Q000378:metabolism; D004224:Diterpenes; D004464:Econazole / Q000494:pharmacology; D046934:Ginkgolides; D006454:Hemoglobins / Q000032:analysis; D006470:Hemorrhage / Q000209:etiology; D007213:Indomethacin / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism; D015289:Leukotrienes / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000502:physiology*; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013931:Thromboxanes / Q000037:antagonists & inhibitors; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D004224:Diterpenes; D046934:Ginkgolides; D006454:Hemoglobins; D007783:Lactones; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D011422:Propionates; D011804:Quinolines; D013931:Thromboxanes; D014230:Triazoles; C052518:WEB 2086; D007975:Leukotriene B4; C059141:verlukast; D004464:Econazole; C045856:ginkgolide B; D015232:Dinoprostone; D007213:Indomethacin