Ligation of lymphocyte function-associated antigen-1 on monocytes decreases very late antigen-4-mediated adhesion through a reactive oxygen species-dependent pathway.
Monocyte-endothelial adhesion plays an important role in monocyte trafficking and hence is important for immune responses and pathogenesis of inflammatory diseases including atherosclerosis. The cross-talk between different integrins on monocytes may be crucial for a coordinated regulation of the cellular adhesion during the complex process of transendothelial migration. By using monoclonal antibodies and recombinant intercellular adhesion molecule 1 (ICAM-1) to engage lymphocyte function-associated antigen 1 (LFA-1) on monocytic cells, we found that the cellular adhesion to vascular cell adhesion molecule 1 (VCAM-1) mediated by very late antigen 4 (VLA-4) was suppressed after this treatment and the suppression depended on the presence of reactive oxygen species (ROSs). Inhibition of production of ROSs through the use of inhibitor of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, but not inhibitors of mitochondrial electron transport chain or xanthine oxidase, revealed that this suppression on VLA-4-mediated cellular binding was mediated by ROSs produced by phagocyte NADPH oxidase. Activation of phosphoinositol-3 kinase and Akt appears to mediate this NADPH oxidase activation through p47phox phosphorylation and Rac-1 activation. Our results provide a novel pathway in which ROSs play a critical role in integrin cross-talk in monocytes. This signaling pathway may be important for cellular transition from firm arrest to diapedesis during monocyte trafficking.
Institute of Basic Medicine, Department of Pediatrics, National Cheng-Kung University Medical College, 138 Sheng-Li Rd, Tainan 704, Taiwan.
Kuo-Pin
KP
Chuang
Ya-Fang
YF
Huang
Yi-Ling
YL
Hsu
Hsiao-Sheng
HS
Liu
Hong-Chen
HC
Chen
Chi-Chang
CC
Shieh
D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000276:immunology*; D006801:Humans; D039041:Integrin alpha4beta1 / Q000032:analysis / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000502:physiology*; D009000:Monocytes / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000276:immunology*; D011994:Recombinant Proteins / Q000378:metabolism; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D000911:Antibodies, Monoclonal; D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1