Role of third N-terminal domain of VCAM-1

The interaction between VLA-4 and VCAM-1 has been implicated in the recruitment, adhesion, and activation of mononuclear leukocytes in chronic inflammatory conditions and autoimmune disease. The seven domain extracellular portion of VCAM-1, sVCAM1-7, and the first three and two N-terminal domains of VCAM-1, sVCAM1-3 and sVCAM1-2, respectively, were expressed in baculovirus and purified. Using these purified soluble forms of VCAM-1 and cellular transfectants expressing various cell bound forms of VCAM-1, we show that the major binding site for VLA-4 is located within the first two domains of VCAM-1 and that the third domain of VCAM-1 appears to be required for functional integrity of the VLA-4 binding site.