TY - JOUR
T1 - Gαi2 is required for chemokine-induced neutrophil arrest
AU - Zarbock, Alexander
AU - Deem, Tracy L.
AU - Burcin, Tracy L.
AU - Ley, Klaus
PY - 2007/11/15
Y1 - 2007/11/15
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2007-06-094565
DO - 10.1182/blood-2007-06-094565
M3 - Article
C2 - 17699741
AN - SCOPUS:36349025935
SN - 0006-4971
VL - 110
SP - 3773
EP - 3779
JO - Blood
JF - Blood
IS - 10
ER -