PMID: 7521763Jun 1, 1994Paper

Activation dependent and independent VLA-4 binding sites on vascular cell adhesion molecule-1

Cell Adhesion and Communication
L A NeedhamJ Clements

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

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Citations

Nov 15, 2002·Molecular Immunology·Joan M Cook-Mills
Mar 1, 1997·British Journal of Pharmacology·M M Teixeira, P G Hellewell
Feb 13, 2001·British Journal of Pharmacology·M M TeixeiraP G Hellewell
Sep 9, 1998·American Journal of Respiratory Cell and Molecular Biology·A Burke-Gaffney, P G Hellewell
Jan 20, 2007·European Journal of Pharmacology·Hiromi OkigamiKevin B Bacon
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Aug 15, 2002·American Journal of Physiology. Cell Physiology·Margaret Colden-Stanfield
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Jan 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anne Burke-GaffneyPaul G Hellewell
Aug 22, 2006·The Journal of Biological Chemistry·Karin M KirschnerHolger Scholz

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