Activation of leukocyte integrins is important for selective recruitment of cells from the circulation to tissues. Our previous studies showed that the binding between the integrin very late antigen-4 (VLA-4) and vascular cell adhesion molecule-1 (VCAM-1) is modulated by reactive oxygen species. In this study, we investigated the molecular nature of redox modulation on the activation states of VLA-4 on. human leukocytes. We found that ligand binding of VLA-4 induced exposure of sulfhydryl groups on the 帢4 peptide. Low concentrations (5-10 弮M) of exogenous hydrogen peroxide in the presence or absence of added glutathione enhanced the ligand binding ability of VLA-4 to VCAM-1. and cell rolling on VCAM-1, while higher concentrations (??00 弮M) of hydrogen peroxide inhibited the binding. Exogenous hydrogen peroxide and glutathione induced molecular modification of S-glutathionylation on the 帢4 peptide. The redox regulation of the VLA-4 binding activity required outside-in signaling and cytoskeleton rearrangement. Our results indicate that ligand binding of VLA-4 involves redox modulations which may play a pivotal role in regulating the activation states of VLA-4 in inflammatory tissues and hence direct leukocyte trafficking. 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Date:
2008-02
Relation:
European Journal of Immunology. 2008 Feb;38(2):410-423.
