Galphai2 is required for chemokine-induced neutrophil arrest.
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.
Zarbock
Alexander
A
Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908-1394, USA.
Deem
Tracy L
TL
Burcin
Tracy L
TL
Ley
Klaus
K
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
D018925:Chemokines; D008070:Lipopolysaccharides; D013864:Thioglycolates; D010738:Type C Phospholipases; D051960:GTP-Binding Protein alpha Subunit, Gi2
J Immunol. 2000 Mar 15;164(6):3301-8
10706723
Immunity. 2007 Jun;26(6):773-83
17543554
Immunity. 2000 Dec;13(6):759-69
11163192
Am J Physiol Cell Physiol. 2001 Nov;281(5):C1568-78
11600420
Blood. 2001 Dec 1;98(12):3309-14
11719368
Methods Enzymol. 2002;344:277-98
11771389
Immunol Rev. 2002 Aug;186:8-18
12234358
Cell. 2002 Sep 20;110(6):673-87
12297042
J Clin Invest. 2002 Dec;110(11):1703-16
12464676
Blood. 2003 May 15;101(10):4155-63
12531806
Immunity. 2004 Apr;20(4):393-406
15084269
Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10060-5
15220478
J Cell Biol. 2004 Jul 19;166(2):273-82
15249579
Science. 2000 Feb 11;287(5455):1049-53
10669418
J Exp Med. 2004 Oct 4;200(7):935-9
15466624
Microvasc Res. 1978 Jan;15(1):93-101
634160
J Exp Med. 1985 Jul 1;162(1):145-56
2989409
Science. 1989 Jul 14;245(4914):183-6
2749255
J Pharmacol Exp Ther. 1990 May;253(2):688-97
2338654
J Pharmacol Exp Ther. 1990 Nov;255(2):756-68
2147038
J Cell Physiol. 1990 Nov;145(2):295-302
2174064
Cell. 1991 Dec 20;67(6):1033-6
1760836
Nature. 1992 Dec 17;360(6405):684-6
1465133
Nat Genet. 1992 May;1(2):85-91
1302014
Science. 1993 Jul 2;261(5117):101-3
8316840
J Immunol. 1993 Dec 1;151(11):6347-57
7504019
Cell. 1994 Jan 28;76(2):301-14
7507411
J Immunol. 1994 Feb 1;152(3):1370-9
8301138
J Exp Med. 1995 Feb 1;181(2):669-75
7530761
J Biol Chem. 1996 Jun 7;271(23):13430-4
8662841
Am J Physiol. 1997 Jan;272(1 Pt 2):H114-22
9038929
Br J Pharmacol. 1997 Mar;120(5):841-50
9138690
Microvasc Res. 1997 Sep;54(2):188-91
9327391
Science. 1998 Jan 16;279(5349):381-4
9430588
Immunity. 2005 Mar;22(3):285-94
15780986
Immunity. 2005 Mar;22(3):343-54
15780991
Physiol Rev. 2005 Oct;85(4):1159-204
16183910
Am J Physiol Lung Cell Mol Physiol. 2005 Nov;289(5):L807-15
15951336
Microcirculation. 2006 Mar;13(2):99-109
16459323
J Clin Invest. 2006 Mar;116(3):695-702
16485040
Thromb Haemost. 2006 Jan;95(1):5-11
16543955
J Immunol. 2006 Jul 1;177(1):604-11
16785558
Immunity. 2006 Aug;25(2):185-7
16920634
J Leukoc Biol. 2006 Dec;80(6):1491-9
16997858
J Clin Invest. 2006 Dec;116(12):3211-9
17143330
Blood. 2007 Jan 1;109(1):176-84
16960156
Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4371-6
17360531
Immunity. 2007 Apr;26(4):477-89
17442598
Am J Respir Crit Care Med. 2007 May 15;175(10):1027-35
17322107
J Immunol. 2007 Jul 1;179(1):439-48
17579064
Circ Res. 2000 Nov 10;87(10):903-9
11073886