Gαi2 is required for chemokine-induced neutrophil arrest
Open Access
- 15 November 2007
- journal article
- Published by American Society of Hematology in Blood
- Vol. 110 (10), 3773-3779
- https://doi.org/10.1182/blood-2007-06-094565
Abstract
Chemokines, including CXCL1, participate in neutrophil recruitment by triggering the activation of integrins, which leads to arrest from rolling. The downstream signaling pathways which lead to integrin activation and neutophil arrest following G-protein–coupled receptor engagement are incompletely understood. To test whether Gαi2 is involved, mouse neutrophils in their native whole blood were investigated in mouse cremaster postcapillary venules and in flow chambers coated with P-selectin, ICAM-1, and CXCL1. Gnai2−/− neutrophils showed significantly reduced CXCL1-induced arrest in vitro and in vivo. Similar results were obtained with leukotriene B4 (LTB4). Lethally irradiated mice reconstituted with Gnai2−/− bone marrow showed a similar defect in chemoattractant-induced arrest as that of Gnai2−/− mice. In thioglycollate-induced peritonitis and lipopolysaccaride (LPS)–induced lung inflammation, chimeric mice lacking Gαi2 in hematopoietic cells showed about 50% reduced neutrophil recruitment similar to that seen in Gnai2−/− mice. These data show that neutrophil Gαi2 is necessary for chemokine-induced arrest, which is relevant for neutrophil recruitment to sites of acute inflammation.Keywords
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