التفاصيل البيبلوغرافية
| العنوان: |
Integrin activation by P-Rexl is required for selectin-mediated slow leukocyte rolling and intravascular crawling. |
| المؤلفون: |
Herter, Jan M.1,2, Rossaint, Jan1,2, Block, Helena1,2, Welch, Heidi3, Zarbock, Alexander1,2 |
| المصدر: |
Blood. 3/21/2013, Vol. 121 Issue 12, p2301-2310. 10p. |
| مصطلحات موضوعية: |
*SELECTINS, *LEUCOCYTES, *INTEGRINS, *CELL adhesion molecules, *INFLAMMATION, *NUCLEOTIDE exchange factors, *ACUTE kidney failure, *NEUTROPHILS |
| مستخلص: |
Integrin activation is essential for the function of leukocytes. Impaired integrin activation on leukocytes is the hallmark of the leukocyte adhesion deficiency syndrome in humans, characterized by impaired leukocyte recruitment and recurrent infections. In inflammation, leukocytes collect different signals during the contact with the microvasculature, which activate signaling pathways leading to integrin activation and leukocyte recruitment. We report the role of P-Rex1, a Rac-specific guanine nucleotide exchanging factor, in integrin activation and leukocyte recruitment. We find that P-Rexi is required for inducing selectin- mediated lymphocyte function-associated antigen-i (LFA-i) extension that corresponds to intermediate affinity and induces slow leukocyte rolling, whereas P-Rexi is not involved in the induction of the high-affinity conformation of LFA-i obligatory for leukocyte arrest. Furthermore, we demonstrate that P-Rexi is involved in Mac-i-dependent intravascular crawling. In vivo, both LFA-1-dependent slow rolling and Mac-1-dependent crawling are defective in P-Rex-/- leukocytes, whereas chemokine-induced arrest and postadhesion strengthening remain intact in P-Rexi- deficient leukocytes. Raci is involved in E-selectin-mediated slow rolling and crawling. In vivo, in an ischemia-reperfusion-induced model of acute kidney injury, abolished selectin-mediated integrin activation contributed to decreased neutrophil recruitment and reduced kidney damage in P-Rexi-deficient mice. We conclude that P-Rexi serves distinct functions in LFA-i and Mac-i activation. (Blood. 20i3;121(12):230i-23i0) [ABSTRACT FROM AUTHOR] |
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