INVOLVEMENT OF THE COMPLEMENT-SYSTEM IN THE PATHOGENESIS OF PULMONARYLEUKOSTASIS IN EXPERIMENTAL MYELOCYTIC-LEUKEMIA

The role of the complement system in the pathogenesis of pulmonary leu kostasis in myelocytic leukemia was studied in a rat model. Acute myel ocytic leukemia was induced in six Brown-Norway rats, and complement l evels were assayed during the course of the disease. Whole complement activity (CH50) and hemolytic activity of C1q, C3, and C4 decreased fr om day 1 6 after induction of the leukemia, when the rats developed pu lmonary leukostasis. In addition, local complement activation was esta blished in the lung vessels by immunofluorescence microscopy in advanc ed stages of pulmonary leukostasis. Finally, following systemic activa tion of the complement system by injection of cobra venom factor (CVF) , leukemic rats (n = 6) died of pulmonary leukostasis 4.5 days earlier than did leukemic controls (n = 6). These findings suggest that, in a cute myelocytic leukemia in Brown-Norway rats, pulmonary leukostasis i s induced by activation of the complement system. This finding could l ead to new modes of treatment for a life-threatening complication of l eukemia.