Tissue fibrin deposition during acute lung injury in rabbits and its relationship to local expression of procoagulant and fibrinolytic activities.
Parenchymal fibrin deposition is well recognized in many forms of acute lung injury. Proteins derived from the actions of the coagulation and fibrinolytic systems may potentiate these inflammatory reactions as well as influence the subsequent repair process. However, the factors regulating fibrin formation and dissolution in acute pneumonitis have not been defined. In this study, we characterized the procoagulant (PC) and fibrinolytic activities simultaneously present in the alveolar space during the course of acute lung injury induced in rabbits by an intravenous injection of phorbol myristate acetate (PMA). Within 6 h of PMA injection, this injury was characterized histologically by extensive intra-alveolar fibrin formation and marked accumulation in pulmonary parenchyma of intravenously administered 125I-fibrinogen. Clearance of fibrin ensued over the remainder of the 72-h study period. Normal BAL fluid contained high levels of procoagulant activity which did not vary after the onset of inflammation. The procoagulant activity was attributed to particle-bound tissue thromboplastin as well as other factors of the extrinsic coagulation pathway. There were low levels of plasminogen activator (PA) activity in normal BAL fluid, but the mean activity increased 9.3-fold over control values by 12 h after PMA injection (p less than 0.01). When plasminogen activator activity in BAL fluid was referenced to the concomitant procoagulant activity, this ratio (PA/PC) increased 17.8-fold over controls, peaking 24 h after PMA injection (p less than 0.01). The levels of both procoagulant and plasminogen activator activities associated with alveolar macrophages were stable during the study period. Compared to alveolar macrophages, granulocytes expressed similar levels of plasminogen activator but negligible procoagulant activity.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001779:Blood Coagulation Factors; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis; D007962:Leukocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D010960:Plasminogen Activators / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D001779:Blood Coagulation Factors; C045071:leukocyte procoagulant activity; C045072:macrophage procoagulant activity; D005337:Fibrin; D010960:Plasminogen Activators; D013755:Tetradecanoylphorbol Acetate