Journal
MOLECULAR IMMUNOLOGY
Volume 48, Issue 12-13, Pages 1408-1416Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2011.03.018
Keywords
Cytohesin-1; Neutrophil; LFA-1; beta 2 Integrins; Adhesion; HUVECs
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Funding
- Canadian Institutes of Health Research
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Cytohesin-1 is a guanine nucleotide exchange factor for ADP ribosylation factor 6 (Arf6) in human blood neutrophils and differentiated PLB-985 neutrophil-like cells. Cytohesin-1 regulates adhesion and the transendothelial migration of monocytes, dendritic cells and T lymphocytes through activation of the beta 2 integrin LFA-1. In this study we investigated the role of cytohesin-1 in neutrophil and neutrophil-like cell adhesion to HUVECs, immobilized ICAM-1, and the alpha 4 beta 1 and alpha 5 beta 1 integrin extracellular matrix ligand fibronectin. We show that cytohesin-1 knockdown or inhibition with secinH3 inhibits fMLF-mediated cell adhesion to HUVECs and immobilized ICAM-1, whereas cytohesin-1 over-expression has the opposing effect. Binding of PLB-985 cells to HUVECs correlated with expression of the high-affinity beta 2 integrin epitope recognized by mAb24. Adhesion to HUVECs was inhibited by soluble ICAM-1, anti-ICAM-1, anti-CD11a and anti-CD18, but not anti-CD11b, blocking antibodies. We also demonstrate that cytohesin-1 knockdown promotes fMLF-mediated cell adhesion to fibronectin whereas cytohesin-1 over-expression has the opposing effect. Crosstalk between beta 1 and beta 2 integrins also exists since inhibition of beta 1 integrin functions with blocking antibodies enhanced adhesion of PLB-985 over-expressing cytohesin-1 to ICAM-1. We suggest that cytohesin-1 is a key regulator of neutrophil adhesion to endothelial cells and to components of extracellular matrix, which may influence cell emigration through its dual opposing effect on beta 2 and beta 1 integrin activation. (C) 2011 Elsevier Ltd. All rights reserved.
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