title: Role of T lymphocytes in angiotensin II-mediated microvascular thrombosis.
abstract: Clinical trials and animal studies have revealed a role for the renin-angiotensin system in the enhanced thrombus development that is associated with hypertension. Because T lymphocytes have been implicated in the vascular dysfunction and blood pressure elevation associated with increased angiotensin II (Ang II) levels, we evaluated the role of the adaptive immune system in mediating the enhanced thrombosis during Ang II-induced hypertension. Light/dye-induced thrombosis was induced in cremaster arterioles of wild-type, immunodeficient Rag-1(-/-), CD8(+), or CD4(+) lymphocyte-deficient and NADPH oxidase (gp91(phox))-deficient mice implanted with an Ang II-loaded pump for 2 weeks. Chronic Ang II infusion enhanced arteriolar thrombosis in wild-type mice but not in Rag-1(-/-), CD4(+) T-cell-deficient, or gp91(phox-/-) mice. CD8(+) T-cell(-/-) mice exhibited partial protection. Adoptive transfer of T cells derived from wild-type or gp91(phox-/-) mice into Rag-1(-/-) restored the prothrombotic phenotype induced by Ang II. T lymphocytes (CD4(+) and, to a lesser extent, CD8(+)) play a major role in mediating the accelerated microvascular thrombosis associated with Ang II-induced hypertension. NADPH oxidase-derived reactive oxygen species, produced by cells other than T lymphocytes, also appear critical for the Ang II-enhanced, T cell-dependent thrombosis response.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Science Center, 1501 Kings Hwy, Shreveport, LA 71130-3932, USA.
authors.forename: Elena Y
authors.initials: EY
authors.lastname: Senchenkova
authors.forename: Janice
authors.initials: J
authors.lastname: Russell
authors.forename: Elvira
authors.initials: E
authors.lastname: Kurmaeva
authors.forename: Dmitry
authors.initials: D
authors.lastname: Ostanin
authors.forename: D Neil
authors.initials: DN
authors.lastname: Granger
mesh_terms: D019264:Adoptive Transfer; D000804:Angiotensin II; D000818:Animals; D003900:Desoxycorticosterone / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation; D019255:NADPH Oxidases / Q000378:metabolism*; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D013927:Thrombosis / Q000139:chemically induced / Q000276:immunology*
chemical_list: D017382:Reactive Oxygen Species; D000804:Angiotensin II; D003900:Desoxycorticosterone; D019255:NADPH Oxidases