Activation dependent and independent VLA-4 binding sites on vascular cell adhesion molecule-1
Abstract
Vascular cell adhesion molecule-1 (VCAM) is a cytokine-inducible member of the immunoglobulin superfamily which binds to the integrin VLA-4. VCAM is expressed predominantly on the vascular endothelium where it is involved in the recruitment of mononuclear cells and lymphocytes to sites of inflammation. Two forms of VCAM containing six and seven Ig domains (VCAM-6d; VCAM-7d) are generated by alternative splicing but the physiological significance of this is unknown. We have utilised VCAM deletion mutants, VCAM-transfected cell lines and monoclonal antibodies to assess the functional importance of the individual VCAM domains. We have identified two binding sites on VCAM-7d located in domains 1 and 4 that are involved in the adhesion of the U937 human myelomonocytic cell line. Adhesion to domain 1 is temperature-independent, inhibited by the anti-VCAM mAbs 4B2 or lE10, and insensitive to PMA activation. In contrast, adhesion to domain 4 is temperature sensitive, unaffected by mAbs 4B2 or lE10 and augmented by PMA. Adhesion to both domains can be totally inhibited by the anti-VLA-4 mAb, 2B4. The anti-VCAM mAb 4B2 inhibits adhesion of U937 cells to stably transfected VCAM-7d-CHO cells at 4 degrees C, but, at 37 degrees C the effect ...Continue Reading
References
Characterization of the adhesion of the human monocytic cell line U937 to cultured endothelial cells
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