title: Expression and kinetics of induced procoagulant activity in bovine pulmonary alveolar macrophages.
abstract: Leukocytes, especially macrophages, are important cellular mediators of fibrin deposition and removal at tissue sites of inflammation. Pulmonary fibrin deposition is a prominent feature of bovine acute lung injury; therefore, we studied the resting and stimulated procoagulant responses of bovine pulmonary alveolar macrophages (PAM) and peripheral blood neutrophils (PMN). Freshly isolated normal PAM and PMN expressed negligible procoagulant activity. PAM stimulated with endotoxin lipopolysaccharide (LPS), 4 beta-phorbol 12-myristate 13-acetate (PMA) and bovine recombinant interleukin-1 beta (rBIL-1 beta) exhibited protein synthesis- and dose-dependent enhancement of procoagulant activity in 8-h cultures. Bovine recombinant granulocyte macrophage-colony stimulating factor (rBGM-CSF) and recombinant human gamma-interferon (rHIFN-gamma) did not induce procoagulant activity. The kinetics of LPS- and PMA-enhanced PAM procoagulant activity differed: LPS-induced enhancement developed earlier and more rapidly than PMA-induced enhancement. Pasteurella haemolytica LPS was more potent than Escherichia coli LPS in enhancing PAM procoagulant activity, while dexamethasone decreased both baseline and LPS- or PMA-stimulated activity by approximately 50%. PAM procoagulant activity resulted from tissue factor expression. Bovine PMN produced negligible procoagulant activity when stimulated, and are thus unlikely to be major contributors to procoagulant activity in bovine lung. Activity inhibitory to bovine tissue factor was present in both calf and adult sera, and was partly dependent on the presence of factor X for activity. Rapid induction of bovine PAM procoagulant activity by inflammatory mediators, and subsequent resistance to degradation, may thus combine to promote an alveolar microenvironment permissive to fibrin deposition in bovine acute lung injury.
authors.affiliation: Department of Pathology, College of Veterinary Medicine, Cornell University, Ithaca, New York.
authors.forename: B D
authors.initials: BD
authors.lastname: Car
authors.forename: D O
authors.initials: DO
authors.lastname: Slauson
authors.forename: M M
authors.initials: MM
authors.lastname: Suyemoto
authors.forename: M
authors.initials: M
authors.lastname: Doré
authors.forename: N R
authors.initials: NR
authors.lastname: Neilsen
mesh_terms: D000818:Animals; D001779:Blood Coagulation Factors / Q000378:metabolism*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002417:Cattle; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D005167:Factor VII / Q000032:analysis / Q000037:antagonists & inhibitors; D007700:Kinetics; D008074:Lipoproteins / Q000032:analysis; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D013925:Thromboplastin / Q000032:analysis / Q000037:antagonists & inhibitors
chemical_list: D001779:Blood Coagulation Factors; D016207:Cytokines; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005167:Factor VII; D013925:Thromboplastin