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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.

SUBMITTER: Hurley A 

PROVIDER: S-EPMC3549602 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Enhanced effector function of CD8(+) T cells from healthy controls and HIV-infected patients occurs through thrombin activation of protease-activated receptor 1.

Hurley Amanda A   Smith Mindy M   Karpova Tatiana T   Hasley Rebecca B RB   Belkina Natalya N   Shaw Stephen S   Balenga Nariman N   Druey Kirk M KM   Nickel Erin E   Packard Beverly B   Imamichi Hiromi H   Hu Zonghui Z   Follmann Dean D   McNally James J   Higgins Jeanette J   Sneller Michael M   Lane H Clifford HC   Catalfamo Marta M  

The Journal of infectious diseases 20121129 4


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  ...[more]

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