VLA - 4

VLA-4 (Very Late Antigen-4, CD49d/CD29) is expressed by most leukocytes but it is observed on neutrophils only under special conditions. It binds to fibronectin and the immunoglobulin superfamily member VCAM-1. VCAM-1 binding occurs with approximately four times greater affinity than binding to fibronectin. The involvement of VLA-4 in transmigration in vitro is variable. It is likely this reflects redundancy with b2-integrins, as well as the degree of VCAM-1 expression on endothelium, which in turn reflects the state of endothelial activation. It appears unimportant in neutrophil transmigration in vitro (Hakkert et al 1991), and in transmigration of activated T-cells (Oppenheimer Marks et al 1991). VLA-4 antibodies do not reduce transmigration of resting T-cells across resting endothelium nor do they reduce transmigration of monocytes across resting endothelium (Oppenheimer Marks et al 1991; Chuluyan et al 1995; Meerschaert et al 1994; Meerschaert et al 1995). Resting T-cell and NK cell cytokine-activated transmigration are reduced by 40% and 30% respectively (Oppenheimer Marks et al 1991; Bianchi et al 1993). As firm adhesion is reduced to a similar extent it is unclear whether this is a specific effect on passage across the endothelium.

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