title: Platelets can enhance vascular permeability.
abstract: Platelets survey blood vessels, searching for endothelial damage and preventing loss of vascular integrity. However, there are circumstances where vascular permeability increases, suggesting that platelets sometimes fail to fulfill their expected function. Human inflammatory arthritis is associated with tissue edema attributed to enhanced permeability of the synovial microvasculature. Murine studies have suggested that such vascular leak facilitates entry of autoantibodies and may thereby promote joint inflammation. Whereas platelets typically help to promote microvascular integrity, we examined the role of platelets in synovial vascular permeability in murine experimental arthritis. Using an in vivo model of autoimmune arthritis, we confirmed the presence of endothelial gaps in inflamed synovium. Surprisingly, permeability in the inflamed joints was abrogated if the platelets were absent. This effect was mediated by platelet serotonin accumulated via the serotonin transporter and could be antagonized using serotonin-specific reuptake inhibitor antidepressants. As opposed to the conventional role of platelets to microvascular leakage, this demonstration that platelets are capable of amplifying and maintaining permeability adds to the rapidly growing list of unexpected functions for platelets.
authors.affiliation: Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l'Université Laval, Québec, QC, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cloutier
authors.forename: Alexandre
authors.initials: A
authors.lastname: Paré
authors.forename: Richard W
authors.initials: RW
authors.lastname: Farndale
authors.forename: H Ralph
authors.initials: HR
authors.lastname: Schumacher
authors.forename: Peter A
authors.initials: PA
authors.lastname: Nigrovic
authors.forename: Steve
authors.initials: S
authors.lastname: Lacroix
authors.forename: Eric
authors.initials: E
authors.lastname: Boilard
mesh_terms: D000818:Animals; D001168:Arthritis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001327:Autoimmune Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D002199:Capillary Permeability / Q000235:genetics / Q000502:physiology*; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007596:Joints / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
chemical_list: D012701:Serotonin