Prevention by granulocyte depletion of increased vascular permeability of sheep lung following endotoxemia

cytes are necessary for the lung vascular reaction to endotoxin, we measured the endotoxin response in chronically instrumented sheep before and after granulocyte depletion with hydroxyurea. Granulo-cyte depletion did not affect the pulmonary hyper-tension caused by endotoxin (peak mean pulmonary artery pressures = 38+2 cm H20 before depletion and 42+2 after depletion, P = NS). The late phase in-crease in lung lymph flow after endotoxin was signifi-cantly lower in the granulocytopenic animals as re-flected by lung lymph flow (mean steady state lymph flow before depletion = 30.6+2.0 SE ml/h; mean steady state lymph flow after granulocyte depletion = 15.4+1.0; P < 0.01) even though late phase pul-monary vascular pressures were similar before and after granulocyte depletion. Lung lymph protein clearance (lymph flow x lymph/plasma protein concentration) was also significantly lower after granulocyte deple-tion (mean steady state before depletion = 21.4 + 1.4 SE ml/h; and after depletion = 10.4+ 1.0; P < 0.01). We conclude that circulating granulocytes are necessary for the development of increased lung vascular permea-bility to fluid and protein following endotoxin. The pulmonary vasopressor effects of endotoxin in sheep are independent of granulocytes