Leukocytes, platelets, and thromboxane A2 in endotoxin-induced lung injury.

The relationship of leukocytes, platelets, and thromboxane A2 (TxA2) to endotoxin-induced lung injury was studied by use of chronic pulmonary lymph fistula in 12 adult female sheep. Endotoxin-induced lung injury in sheep was characterized by an early pulmonary hypertensive phase followed by a phase of increased capillary permeability. A profound leukopenia occurred early after endotoxin infusion and persisted during both phases of the injury. TxA2 levels (measured as its metabolite thromboxane B2) were significantly increased during the hypertensive phase and then returned rapidly to baseline. Levels were higher in lymph than in plasma, implying local generation in lung. Platelet count decreased transiently later in the permeability phase, rapidly returning toward baseline in animals that survived. The decrease in platelets occurred after TxA2 levels had returned to baseline, suggesting that TxA2 may be coming from sources other than platelets. We conclude that leukocytes appear to play a major role in initiating endotoxin-induced lung injury, and TxA2 may be contributing to pulmonary hypertension. Platelets, on the other hand, seem to be transiently sticking to an already damaged endothelium, with the degree of sequestration indicative of the severity of the injury.