MODULATION OF ENDOTHELIAL-CELL ADHESION BY HEVIN, AN ACIDIC PROTEIN ASSOCIATED WITH HIGH ENDOTHELIAL VENULES

High endothelial venules (HEV) are specialized plump postcapillary ven ules in lymphoid tissues that support high levels of lymphocyte extrav asation from the blood. We have recently identified a novel human tran script, expressed to high levels in HEV, that encodes a secreted, acid ic protein closely related to the anti-adhesive extracellular matrix p rotein known as BM-40, osteonectin, and SPARC (secreted protein acidic and rich in cysteine). Here, we show that this protein, designated he vin, is associated with basal, lateral, and apical surfaces of HEV cel ls, and unlike MECA-79 antigen, is not expressed on the underlying bas ement membrane. In contrast to fibronectin or other adhesive extracell ular matrix proteins, purified hevin does not support endothelial cell adhesion in vitro. Moreover, addition of soluble exogenous hevin inhi bits attachment and spreading of endothelial cells on fibronectin subs trates. Hevin-treated cells do not form focal adhesions and exhibit a rounded morphology. Together, these results suggest that hevin is an a bundant extracellular protein that modulates high endothelial cell adh esion to the basement membrane.