title: The significance of human monocyte thrombomodulin during membrane vesiculation and after stimulation by lipopolysaccharide.
abstract: Thrombomodulin acts as an essential membrane cofactor of thrombin in the triggering of the natural anticoagulant protein C pathway responsible for the inactivation of procoagulant cofactors VIIIa and Va. Because monocytes play a critical role in the coupling between infection/inflammation and thrombosis, the fate of monocyte thrombomodulin was assessed at the cell plasma membrane and on derived microparticles. A significant basal level of thrombomodulin activity was measured on unstimulated monocytes and microparticles. Lipopolysaccharide treatment resulted in increased thrombomodulin activity on monocytes (approximately 40%) and microparticles (approximately 80%), whereas tissue factor and prothrombinase activities were strongly expressed on both. Flow cytometry detection of thrombomodulin antigen confirmed its presence on unstimulated monocytes and microparticles. A decrease (approximately 30%) in thrombomodulin labelling was noticed on stimulated monocytes. Labelling of microparticles shed from stimulated and unstimulated monocytes remained unchanged, only an increased proportion of microparticles (approximately 20%) was observed. The absence of early down-regulation of thrombomodulin following monocyte stimulation suggests that it fulfils an important regulatory function of membrane-associated procoagulant activities. This would be of particular significance at the surface of microparticles having the ability to diffuse and concentrate by adherence at inflammatory sites.
authors.affiliation: Institut d'Hematologie et d'Immunologie, Faculte de Medecine, Universite Louis Pasteur, Strasbourg, France.
authors.forename: N
authors.initials: N
authors.lastname: Satta
authors.forename: J M
authors.initials: JM
authors.lastname: Freyssinet
authors.forename: F
authors.initials: F
authors.lastname: Toti
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism* / Q000502:physiology; D018180:Thrombomodulin / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D018180:Thrombomodulin; D013925:Thromboplastin