title: Disparate mechanisms of induction of procoagulant activity by live and inactivated bacteria and viruses.
abstract: This study describes the dose response, time course, and lymphocyte requirements of procoagulant activity (PCA) induction following stimulation of thioglycolate-elicited BALB/c peritoneal macrophages with live and inactivated bacteria (Bacteroides fragilis, Escherichia coli, and Staphylococcus aureus) and murine hepatitis virus type 3 (MHV-3). Induction of PCA by MHV-3 was significantly more rapid and the maximal PCA achieved was significantly greater than by the three bacterial species studied. In relation to induction of PCA by bacteria, the PCA response was more rapid and of greater magnitude with S. aureus and E. coli than with B. fragilis. MHV-3 induced an augmented PCA response at all concentrations of virus studied in a dose-dependent fashion, whereas higher titers of live bacteria (greater than 10(7) CFU/ml) inhibited PCA, suggesting the production of an inhibitory factor. Significant PCA induction was observed when macrophages were incubated with bacteria or virus in the absence of lymphocytes. At low titers of B. fragilis (10(3) CFU/ml), addition of lymphocytes greatly augmented PCA production, whereas at higher titers (10(7) CFU/ml), the addition of lymphocytes only slightly augmented the PCA response. In contrast, MHV-3 induction of PCA was enhanced by the addition of lymphocytes at all concentrations of virus studied, suggesting a lymphocyte-dependent process. Heat-inactivated bacteria were as effective as live bacteria in inducing PCA, suggesting that induction of PCA by bacteria requires only a bacterial surface component. In contrast, UV-inactivated MHV-3 did not induce PCA, suggesting that viral replication is a necessary step in PCA induction. These results suggest that the cellular and metabolic requirements for induction of PCA differ among viral and bacterial pathogens and may partly explain their differences in pathogenicity.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: S B
authors.initials: SB
authors.lastname: Sinclair
authors.forename: O D
authors.initials: OD
authors.lastname: Rotstein
authors.forename: G A
authors.initials: GA
authors.lastname: Levy
mesh_terms: D000818:Animals; D001407:Bacillus; D001424:Bacterial Infections / Q000503:physiopathology*; D001779:Blood Coagulation Factors / Q000378:metabolism*; D004926:Escherichia coli; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000502:physiology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus; D013211:Staphylococcus aureus; D013997:Time Factors; D014777:Virus Diseases / Q000503:physiopathology*
chemical_list: D001779:Blood Coagulation Factors; C045072:macrophage procoagulant activity