References
Query Results -- Details
MGI Accession ID: MGI:3718855
J Number: J:123587
Other Accession IDs:
Title: Spleen tyrosine kinase Syk is necessary for E-selectin-induced alpha(L)beta(2) integrin-mediated rolling on intercellular adhesion molecule-1.
Authors: Zarbock A; Lowell CA; Ley K
Journal: Immunity
Volume: 26
Issue: 6
Date: 2007 Jun
Year: 2007
Pages: 773-83
Review Status: Peer Reviewed
Abstract:
Engagement of neutrophils by E-selectin results in integrin activation. Here, we investigated primary mouse neutrophils in whole blood by using intravital microscopy and autoperfused flow chambers. Slow rolling on E-selectin coimmobilized with intercellular adhesion molecule-1 (ICAM-1) required P-selectin glycoprotein ligand (PSGL)-1, was dependent on alpha(L)beta(2) integrin (LFA-1), and required continuous E-selectin engagement. Slow rolling was abolished by pharmacological blockade of spleen tyrosine kinase (Syk) and was absent in Syk(-/-) bone-marrow chimeric mice. Treatment with tumor necrosis factor-alpha lowered rolling velocity further and induced CXC chemokine ligand-1 (CXCL1) and CXC chemokine receptor-2 (CXCR2)-dependent leukocyte arrest on E-selectin and ICAM-1. Arrest but not rolling was blocked by an allosteric inhibitor of LFA-1 activation. Neutrophil recruitment in a thioglycollate-induced peritonitis model was almost completely inhibited in Selplg(-/-) mice or Syk(-/-) bone-marrow chimeras treated with pertussis toxin. This identifies a second neutrophil-activation pathway that is as important as activation through G protein-coupled receptors (GPCRs).
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