Leukotriene B4 increases pulmonary transvascular filtration by a neutrophil-independent mechanism

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.