title: Platelets participate in synovitis via Cox-1-dependent synthesis of prostacyclin independently of microparticle generation.
abstract: In addition to the well-described role of platelets in thrombosis, a growing body of evidence implicates platelets in diverse inflammatory responses. We recently showed platelets can contribute to the pathophysiology of inflammatory arthritis via IL-1- containing microparticles. In this study, we demonstrate that platelets, and not platelet microparticles, actively contribute to synovitis via production of proinflammatory prostacyclin in an autoimmune arthritis model. Using both genetic and pharmacologic approaches, we establish that paracrine production of prostacyclin proceeds in the absence of cyclooxygenase-2. Furthermore, we also demonstrate that prostacyclin generation can arise via transcellular collaboration between platelets and fibroblast-like synoviocytes. In addition to shedding light on an unappreciated pathway of lipid synthesis in arthritis, we further delineate a novel effector activity by which platelets can contribute to inflammatory disease.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. eric.boilard@crchuq.ulaval.ca
authors.forename: Eric
authors.initials: E
authors.lastname: Boilard
authors.forename: Katherine
authors.initials: K
authors.lastname: Larabee
authors.forename: Ruslan
authors.initials: R
authors.lastname: Shnayder
authors.forename: Kathleen
authors.initials: K
authors.lastname: Jacobs
authors.forename: Richard W
authors.initials: RW
authors.lastname: Farndale
authors.forename: Jerry
authors.initials: J
authors.lastname: Ware
authors.forename: David M
authors.initials: DM
authors.lastname: Lee
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000201:enzymology / Q000473:pathology; D001792:Blood Platelets / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D001853:Bone Marrow / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D055252:Cell-Derived Microparticles / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D051545:Cyclooxygenase 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013585:Synovitis / Q000097:blood* / Q000201:enzymology / Q000473:pathology
chemical_list: D011464:Epoprostenol; D051545:Cyclooxygenase 1