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Role of angiotensin II in ischemia/reperfusion‐induced leukocyte‐endothelium interactions in the colon
Author(s) -
Riaz Amjid A.,
Wang Yusheng,
Schramm Rene,
Sato Tohru,
Menger Michael D.,
Jeppsson Bengt,
Thorlacius Henrik
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0502fje
Subject(s) - angiotensin ii , chemokine , chemistry , angiotensin ii receptor type 1 , inflammation , chemotaxis , endothelium , microcirculation , ischemia , leukocyte trafficking , receptor , immunology , medicine , endocrinology
The aims of the present study were to determine the effects and mechanisms of angiotensin II (Ang II) on leukocyte‐endothelium interactions and the role of Ang II in a novel model of ischemia/reperfusion (I/R) in the mouse colon. Ang II dose‐dependently increased leukocyte rolling and adhesion in colonic venules. Importantly, Ang II‐induced leukocyte rolling was completely inhibited by immunoneutralization of P‐selectin, and leukocyte adhesion was abolished in lymphocyte function antigen‐1 (LFA‐1)‐deficient mice. The P‐selectin‐dependent rolling was found to be a precondition for the subsequent LFA‐1‐dependent leukocyte adhesion. Moreover, Ang II‐induced leukocyte responses involved generation of reactive oxygen species and up‐regulation of CXC chemokines. Notably, CXC chemokines, but not Ang II, stimulated leukocyte chemotaxis in vitro. I/R increased gene expression of angiotensin converting enzyme (ACE) in the colon and plasma concentrations of Ang II. Inhibition of ACE and the type 1 angiotensin (AT 1 ) receptor significantly decreased the I/R‐induced leukocyte adhesion. Taken together, these novel findings demonstrate that Ang II exerts potent pro‐inflammatory effects in the colonic microcirculation and that inhibition of Ang II expression or function protects against I/R‐induced leukocyte responses in the colon. Thus, it is suggested that Ang II is a major target to control pathological inflammation in the colon.