title: Platelets enhance endotoxin-induced monocyte tissue factor (TF) activity in the horse.
abstract: Endotoxaemia is the leading cause of death in horses. Disseminated intravascular coagulation (DIG), stimulated by induced monocyte proteins, is a prominent feature. Monocyte-platelet cellular interactions are central to the vascular dysfunction produced by circulating endotoxin and are implicated in many thrombotic diseases in the horse. This study reports that endotoxin (0.01-10 microg ml(-1)) and blood platelets (2.5 x 10(7) - 1 x 10(8) ml(-1)) are potent inducers of expression and activity of monocyte tissue factor (TF), the primary activator of the blood coagulation protease cascade. The co-incubation of endotoxin-stimulated monocytes with platelets resulted in greater production of this protein. Cycloheximide (1 mM) inhibited part of the stimulatory effect of endotoxin and/or platelets, the uninhibited part indicating de-encryption of cell-surface TF. Hence, platelets are considered to be an important component of the endotoxin-stimulated response of equine monocytes. The role of platelets as potent stimulators of endotoxin-stimulated monocyte proteins and mediators in vitro is likely to be of significance in vivo in the clinical manifestations and management of endotoxaemia in the horse.
authors.affiliation: Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CBS OES, UK.
authors.forename: A L
authors.initials: AL
authors.lastname: Ouellette
authors.forename: R J
authors.initials: RJ
authors.lastname: Evans
authors.forename: M F
authors.initials: MF
authors.lastname: Heath
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D019446:Endotoxemia / Q000097:blood / Q000662:veterinary; D004731:Endotoxins / Q000633:toxicity*; D006734:Horse Diseases / Q000097:blood; D006736:Horses / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D013925:Thromboplastin / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004731:Endotoxins; D013925:Thromboplastin; D003513:Cycloheximide