期刊
IMMUNITY
卷 26, 期 6, 页码 773-783出版社
CELL PRESS
DOI: 10.1016/j.immuni.2007.04.011
关键词
-
类别
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL073361, R01HL054136] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R01EB002185] Funding Source: NIH RePORTER
- NHLBI NIH HHS [P01 HL073361, HL 73361, R01 HL054136-08] Funding Source: Medline
- NIBIB NIH HHS [R01 EB002185, R01 EB002185-06A2] Funding Source: Medline
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).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据