CLONING OF AN INFLAMMATION-SPECIFIC PHOSPHATIDYL INOSITOL-LINKED FORMOF MURINE VASCULAR CELL-ADHESION MOLECULE-1

Vascular cell adhesion molecule-1 (VCAM1) is a member of the immunoglo bulin (Ig) superfamily which interacts with the integrin very late ant igen-4 (VLA4). The VCAM1/VLA4 interaction mediates both adhesion and s ignal transduction and is thought to play an important role in inflamm atory and immune responses in vivo. VCAM1 cDNAs cloned from mouse, rat , rabbit, and human libraries contain six, seven, or eight extracellul ar Ig-like domains generated by alternate splicing, but to date shorte r 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-t erminal tail generated by alternate splicing of a previously undescrib ed exon. This truncated form of murine VCAM1 (3D-VCAM1) is expressed i n COS cells as a functional adhesion molecule which is lost from the c ell surface following treatment with phosphatidylinositol-specific pho spholipase C. 3D-VCAM1 is found only in endotoxin-treated but not cont rol murine and rat tissues. Thus in rodents alternate splicing of the VCAM1 gene generates a unique truncated inflammation-specific phosphat idylinositol-linked form of VCAM1.