title: Galphai2 is required for chemokine-induced neutrophil arrest.
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 Galpha(i2) 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 B(4) (LTB(4)). 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 Galpha(i2) in hematopoietic cells showed about 50% reduced neutrophil recruitment similar to that seen in Gnai2(-/-) mice. These data show that neutrophil Galpha(i2) is necessary for chemokine-induced arrest, which is relevant for neutrophil recruitment to sites of acute inflammation.
authors: Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908-1394, USA.
authors: Alexander
authors: A
authors: Zarbock
authors: Tracy L
authors: TL
authors: Deem
authors: Tracy L
authors: TL
authors: Burcin
authors: Klaus
authors: K
authors: Ley
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000494:pharmacology*; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D010538:Peritonitis / Q000139:chemically induced / Q000473:pathology; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology; D013864:Thioglycolates; D010738:Type C Phospholipases / Q000502:physiology; D014699:Venules / Q000378:metabolism / Q000473:pathology
chemical_list: D018925:Chemokines; D008070:Lipopolysaccharides; D013864:Thioglycolates; D010738:Type C Phospholipases; D051960:GTP-Binding Protein alpha Subunit, Gi2
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