Altered CXCR2 Signaling in beta-Arrestin-2-Deficient Mouse Models Export

@article{citeulike:3065315, abstract = {CXCR2 is a G-protein-coupled receptor (GPCR) that binds the CXC chemokines, CXCL1-3 and CXCL5-8, and induces intracellular signals associated with chemotaxis. Many adaptor proteins are actively involved in the sequestration, internalization, and trafficking of CXCR2 and transduction of agonist-induced intracellular signaling. We have previously shown that adaptor protein {beta}-arrestin-2 ({beta}arr2) plays a crucial role in transducing signals mediated through CXCR2. To further investigate the role of {beta}arr2 on CXCR2-mediated signaling during acute inflammation, zymosan-induced neutrophils were isolated from peritoneal cavities of {beta}arr2-deficient ({beta}arr2-/-) and their wild-type ({beta}arr2+/+) littermate mice, and neutrophil CXCR2 signaling activities were determined by measurement of Ca2+ mobilization, receptor internalization, GTPase activity, and superoxide anion production. The results showed that the deletion of {beta}arr2 resulted in increased Ca2+ mobilization, superoxide anion production, and GTPase activity in neutrophils, but decreased receptor internalization relative to wild-type mice. Two animal models, the dorsal air pouch model and the excisional wound healing model, were used to further study the in vivo effects of {beta}arr2 on CXCR2-mediated neutrophil chemotaxis and on cutaneous wound healing. Surprisingly, the recruitment of neutrophils was increased in response to CXCL1 in the air pouch model and in the excisional wound beds of {beta}arr2-/- mice. Wound re-epithelialization was also significantly faster in {beta}arr2-/- mice than in {beta}arr2+/+ mice. Taken together, the data indicate that {beta}arr2 is a negative regulator for CXCR2 in vivo signaling.}, author = {Su, Yingjun and Raghuwanshi, Sandeep K. and Yu, Yingchun and Nanney, Lillian B. and Richardson, Ricardo M. and Richmond, Ann}, citeulike-article-id = {3065315}, citeulike-linkout-0 = {http://www.jimmunol.org/cgi/content/abstract/175/8/5396}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16210646}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16210646}, day = {15}, journal = {J Immunol}, keywords = {cxcr2}, month = {October}, number = {8}, pages = {5396--5402}, posted-at = {2008-07-31 12:07:09}, priority = {2}, title = {Altered CXCR2 Signaling in {beta}-Arrestin-2-Deficient Mouse Models}, url = {http://www.jimmunol.org/cgi/content/abstract/175/8/5396}, volume = {175}, year = {2005} }

TY - JOUR ID - citeulike:3065315 L3 - citeulike-article-id:3065315 N2 - CXCR2 is a G-protein-coupled receptor (GPCR) that binds the CXC chemokines, CXCL1-3 and CXCL5-8, and induces intracellular signals associated with chemotaxis. Many adaptor proteins are actively involved in the sequestration, internalization, and trafficking of CXCR2 and transduction of agonist-induced intracellular signaling. We have previously shown that adaptor protein {beta}-arrestin-2 ({beta}arr2) plays a crucial role in transducing signals mediated through CXCR2. To further investigate the role of {beta}arr2 on CXCR2-mediated signaling during acute inflammation, zymosan-induced neutrophils were isolated from peritoneal cavities of {beta}arr2-deficient ({beta}arr2-/-) and their wild-type ({beta}arr2+/+) littermate mice, and neutrophil CXCR2 signaling activities were determined by measurement of Ca2+ mobilization, receptor internalization, GTPase activity, and superoxide anion production. The results showed that the deletion of {beta}arr2 resulted in increased Ca2+ mobilization, superoxide anion production, and GTPase activity in neutrophils, but decreased receptor internalization relative to wild-type mice. Two animal models, the dorsal air pouch model and the excisional wound healing model, were used to further study the in vivo effects of {beta}arr2 on CXCR2-mediated neutrophil chemotaxis and on cutaneous wound healing. Surprisingly, the recruitment of neutrophils was increased in response to CXCL1 in the air pouch model and in the excisional wound beds of {beta}arr2-/- mice. Wound re-epithelialization was also significantly faster in {beta}arr2-/- mice than in {beta}arr2+/+ mice. Taken together, the data indicate that {beta}arr2 is a negative regulator for CXCR2 in vivo signaling. IS - 8 JF - J Immunol EP - 5402 TI - Altered CXCR2 Signaling in {beta}-Arrestin-2-Deficient Mouse Models VL - 175 SP - 5396 KW - cxcr2 AU - Su, Yingjun AU - Raghuwanshi, Sandeep AU - Yu, Yingchun AU - Nanney, Lillian AU - Richardson, Ricardo AU - Richmond, Ann PY - 2005/10/15/ UR - http://www.jimmunol.org/cgi/content/abstract/175/8/5396 ER -