Journal of Applied Physiology, Vol 74, Issue 5 2174-2179, Copyright © 1993 by American Physiological Society
Leukotriene B4 induces lung injury in the rabbit: role of neutrophils and effect of indomethacin
K. Yoshimura, S. Nakagawa, S. Koyama, T. Kobayashi and T. Homma
Institute of Cardiovascular Diseases, Shinshu University School of Medicine, Matsumoto, Japan.
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.
