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The significance of human monocyte thrombomodulin during membrane vesiculation and after stimulation by lipopolysaccharide
Author(s) -
SATTA NATHALIE,
FREYSSINET JEANMARIE,
TOTI FLORENCE
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.d01-2059.x
Subject(s) - thrombomodulin , monocyte , lipopolysaccharide , thrombin , tissue factor , platelet , chemistry , flow cytometry , inflammation , protein c , immunology , prothrombinase , microbiology and biotechnology , medicine , biochemistry , biology , coagulation
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 (∼40%) and microparticles (∼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 (∼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 (∼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.