Cloning of an inflammation-specific phosphatidyl inositol-linked form of murine vascular cell adhesion molecule-1

Abstract

Vascular cell adhesion molecule-1 (VCAM1) is a member of the immunoglobulin (Ig) superfamily which interacts with the integrin very late antigen-4 (VLA4). The VCAM1/VLA4 interaction mediates both adhesion and signal transduction and is thought to play an important role in inflammatory and immune responses in vivo. VCAM1 cDNAs cloned from mouse, rat, rabbit, and human libraries contain six, seven, or eight extracellular Ig-like domains generated by alternate splicing, but to date shorter forms have not been found. We have cloned a novel cDNA encoding only the three N-terminal domains of murine VCAM1 followed by a unique C-terminal tail generated by alternate splicing of a previously undescribed exon. This truncated form of murine VCAM1 (3D-VCAM1) is expressed in COS cells as a functional adhesion molecule which is lost from the cell surface following treatment with phosphatidylinositol-specific phospholipase C. 3D-VCAM1 is found only in endotoxin-treated but not control murine and rat tissues. Thus in rodents alternate splicing of the VCAM1 gene generates a unique truncated inflammation-specific phosphatidylinositol-linked form of VCAM1.