Leukocyte sequestration in pulmonary microvessels and lung injury following systemic complement activation in rabbits

Inflammatory reactions are associated with sequestration of leukocytes in t he lung. Complement activation leads to accumulation of leukocytes in alveo lar septa and alveoli, to lung edema and hemorrhage. Although in organs oth er than the lung leukocytes interact with the vascular endothelium only in postcapillary venules, alveolar capillaries are considered to be the site o f leukocyte sequestration in the lung. However, pulmonary venules and arter ioles have not been investigated systematically after complement activation so far, A closed thoracic window was implanted in anesthetized rabbits; le ukocytes and red blood cells were stained, and the movement of these cells was measured in superficial pulmonary arterioles, venules and alveolar capi llaries using fluorescence video microscopy before and 30 and 60 min after infusion of cobra venom factor (CVF). Erythrocyte velocity and macrohemodyn amic conditions did not change after CVF infusion and were not different fr om the sham-treated controls. The number of sticking leukocytes increased s ignificantly compared to baseline and control: by 150% in arterioles and in venules and by 740% in alveolar capillaries within 60 min after CVF infusi on. The width of alveolar septa in vivo was significantly enlarged after CV F infusion, indicating interstitial pulmonary edema. At the end of the expe riments, myeloperoxidase activity was higher in the CVF group, showing leuk ocyte sequestration in the whole organ. It is concluded that complement act ivation by CVF induces leukocyte sequestration in lung arterioles, venules and alveolar capillaries and leads to mild lung injury.