title: Enhanced effector function of CD8(+) T cells from healthy controls and HIV-infected patients occurs through thrombin activation of protease-activated receptor 1.
abstract: Disruption of vascular integrity by trauma and other tissue insults leads to inflammation and activation of the coagulation cascade. The serine protease thrombin links these 2 processes. The proinflammatory function of thrombin is mediated by activation of protease-activated receptor 1 (PAR-1). We found that peripheral blood effector memory CD4(+) and CD8(+) T lymphocytes expressed PAR-1 and that expression was increased in CD8(+) T cells from human immunodeficiency virus (HIV)-infected patients. Thrombin enhanced cytokine secretion in CD8(+) T cells from healthy controls and HIV-infected patients. In addition, thrombin induced chemokinesis, but not chemotaxis, of CD8(+) T cells, which led to structural changes, including cell polarization and formation of a structure rich in F-actin and phosphorylated ezrin-radexin-moesin proteins. These findings suggest that thrombin mediates cross-talk between the coagulation system and the adaptive immune system at sites of vascular injury through increased T-cell motility and production of proinflammatory cytokines.
authors.affiliation: CMRS/Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1360, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Hurley
authors.forename: Mindy
authors.initials: M
authors.lastname: Smith
authors.forename: Tatiana
authors.initials: T
authors.lastname: Karpova
authors.forename: Rebecca B
authors.initials: RB
authors.lastname: Hasley
authors.forename: Natalya
authors.initials: N
authors.lastname: Belkina
authors.forename: Stephen
authors.initials: S
authors.lastname: Shaw
authors.forename: Nariman
authors.initials: N
authors.lastname: Balenga
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Druey
authors.forename: Erin
authors.initials: E
authors.lastname: Nickel
authors.forename: Beverly
authors.initials: B
authors.lastname: Packard
authors.forename: Hiromi
authors.initials: H
authors.lastname: Imamichi
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Hu
authors.forename: Dean
authors.initials: D
authors.lastname: Follmann
authors.forename: James
authors.initials: J
authors.lastname: McNally
authors.forename: Jeanette
authors.initials: J
authors.lastname: Higgins
authors.forename: Michael
authors.initials: M
authors.lastname: Sneller
authors.forename: H Clifford
authors.initials: HC
authors.lastname: Lane
authors.forename: Marta
authors.initials: M
authors.lastname: Catalfamo
mesh_terms: D001777:Blood Coagulation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D044463:Receptor, PAR-1 / Q000378:metabolism*; D013917:Thrombin / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D044463:Receptor, PAR-1; D013917:Thrombin