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 fragiis, 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 (>107 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. fragiis (103 CFU/ml), addition of lymphocytes greatly augmented PCA production, whereas at higher titers (107 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. 1821 on July 16, 2020 by guest

Platelet-activating factor modulates endotoxin-induced macrophage procoagulant activity by a protein kinase C-dependent mechanism

“…Increased vascular permeability may expose contact factors of plasma to activators, such as collagen, in the extravascular space. In addition, cells of monocyte-macrophage lineage are known to express PCA on their cell surface in response to a variety of inflammatory stimuli, including endotoxin (24), immune complexes (34), and proteolytic products of the complement cascade (28), as well as several microbial pathogens (12,35,39,43).…”

Induction of procoagulant activity on human endothelial cells by Streptococcus pneumoniae

“…The assay was used over the range of 1 to 10,000 mU of PCA, with this range being linear with normal plasma substrate. Previous studies have shown that PCA induced by bacteria and endotoxin are tissue factor-like activities, making comparison with a thromboplastin standard appropriate (13,14).…”

Histopathology of a granulomatous lobular panniculitis in acute Q fever: a case report

“…The pathogenesis of the fibrin‐ring is not well established, but in vitro studies have shown that histiocytes stimulated by infection produce a procoagulant activity substance leading to the formation of long needles of fibrin on the surface of monocytes and macrophages 29,30 . The evolutionary sequence of the different granulomatous patterns remains speculative but Travis 21 noticed in bone marrow biopsies that doughnut granulomas persisted in untreated patients, until at least two month after the onset of the symptoms, even after other types of granulomas were no longer present.…”