Journal of Applied Physiology, Vol 68, Issue 3 1260-1264, Copyright © 1990 by American Physiological Society
Leukotriene B4 increases pulmonary transvascular filtration by a neutrophil-independent mechanism
C. A. Burgess, B. K. McCandless, J. A. Cooper and A. B. Malik
Department of Physiology and Cell Biology, Albany Medical College of Union University, New York 12208.
We examined the role of circulating granulocytes in the pulmonary
microvascular response to leukotriene B4 (LTB4) by prior depletion of
circulating granulocytes using hydroxyurea. LTB4 (2 micrograms/kg injection
followed by infusion of 2 micrograms/kg over 15 min) produced transient
increases in pulmonary arterial pressure and pulmonary vascular resistance,
indicating that neutrophils were not required for the pulmonary hemodynamic
effects of LTB4. Infusion of LTB4 in granulocyte-depleted sheep also
resulted in transient increases in pulmonary lymph flow (QL) with no
significant change in the lymph-to-plasma protein concentration ratio
(L/P), findings similar to those in control animals. In vitro studies
indicated that LTB4 (10(-7) or 10(-9) M) produced a transient adherence of
neutrophils to cultured pulmonary artery endothelial monolayers. Maximal
responses occurred at 10 min after the addition of LTB4 to the endothelial
cell-neutrophil coculture system, and the adherence decreased to base line
within 60 min. LTB4 infusion in sheep also produced a transient uptake of
autologous 111In-oxine-labeled neutrophils. The results indicate that
LTB4-mediated increase in pulmonary transvascular protein clearance (QL x
L/P) is independent of circulating granulocytes.
