Ligation of lymphocyte function-associated antigen-1 on monocytes decreases very late antigen-4-mediated adhesion through a reactive oxygen species-dependent pathway

Kuo Pin Chuang, Ya Fang Huang, Yi Ling Hsu, Hsiao Sheng Liu, Hong Chen Chen, Chi Chang Shieh

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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 NIADPH 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.

Original languageEnglish
Pages (from-to)4046-4053
Number of pages8
JournalBlood
Volume104
Issue number13
DOIs
Publication statusPublished - 2004 Dec 15

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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