MURINE VCAM-1 - MOLECULAR-CLONING, MAPPING, AND ANALYSIS OF A TRUNCATED FORM

Vascular cell adhesion molecule-1 (VCAM-1) is a member of the Ig super family that shows increased expression in a number of pathologic condi tions. The role of VCAM-1 in human disease remains undefined and murin e models are being extensively studied to help define the importance o f VCAM-1 in inflammatory disorders. We have cloned and characterized t he murine Vcam1 gene including 3 kb of 5'-flanking sequences and mappe d the gene to chromosome 3 near Amy1. cDNA clones isolated from a stim ulated hepatic library were found to encode a truncated form of VCAM-1 (T-VCAM-1) which contains Ig domains 1 through 3 and has a unique alt ernative carboxyl terminus. This form arises by alternative splicing. High level expression of T-VCAM-1 in transfected L cells was sufficien t to support adhesion of lymphocytes, and this adhesion was blocked by Abs to VCAM-1. Treatment of transfected COS cells with phospholipase C led to reduced levels of T-VCAM-1 on the cell surface consistent wit h glycosylphosphatidylinositol linkage. Northern blot analysis showed that mRNA for T-VCAM-1 is inducible in multiple tissues after stimulat ion with endotoxin. Both forms of VCAM-1 were expressed in cultured en dothelial, fibroblast, and aortic smooth muscle cells, whereas neither form was observed in monocyte- and lymphocyte-derived lines. Differen tial regulation of both forms of VCAM-1 was observed in the three diff erent cell types that are present in the vessel wall. Thus, expression of VCAM-1 is restricted and controlled at the level of transcription and by alternative splicing.