Leukotriene B4 induces lung injury in the rabbit: role of neutrophils and effect of indomethacin.
The effects of exogenous leukotriene B4 (LTB4) on the pulmonary microvascular permeability and the roles of polymorphonuclear (PMN) leukocytes and the cyclooxygenase products of arachidonic acid in the microvascular response to LTB4 in the isolated non-blood-perfused rabbit lungs were studied. Microvascular permeability and lung edema were evaluated by use of the fluid filtration coefficient (Kf) and the wet-to-dry lung weight ratio (W/D ratio), respectively. Pulmonary capillary pressure was estimated by the double occlusion technique. We studied five groups of lungs: lungs were given 1) both PMN leukocytes and a bolus injection of LTB4 (5 micrograms, n = 6), 2) LTB4 alone (n = 5), 3) PMN leukocytes alone (n = 5), 4) control vehicles (n = 5), or 5) indomethacin (40 micrograms/ml) before PMN leukocytes and LTB4 (n = 6). We observed that LTB4 increased Kf and W/D ratio in the presence of PMN leukocytes in the perfusate without affecting the pulmonary arterial and capillary pressures. Neither LTB4 alone nor PMN leukocytes alone produced changes in Kf and W/D ratio. Indomethacin failed to inhibit the LTB4-induced increases in Kf and W/D ratio. These results suggest that LTB4 produces lung injury that is dependent on PMN leukocytes but not on the cyclooxygenase pathway of arachidonic acid metabolism.
Institute of Cardiovascular Diseases, Shinshu University School of Medicine, Matsumoto, Japan.
K
K
Yoshimura
S
S
Nakagawa
S
S
Koyama
T
T
Kobayashi
T
T
Homma
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000633:toxicity*; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D009929:Organ Size / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000473:pathology / Q000503:physiopathology; D011669:Pulmonary Wedge Pressure / Q000502:physiology; D011817:Rabbits; D012756:Sheep
D007975:Leukotriene B4; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin