MOLECULAR BEHAVIOR ADAPTS TO CONTEXT - HEPARANASE FUNCTIONS AS AN EXTRACELLULAR MATRIX-DEGRADING ENZYME OR AS A T-CELL ADHESION MOLECULE, DEPENDING ON THE LOCAL PH

Migration of lymphocytes into inflammatory sites requires their adhesi on to the vascular endothelium and subendothelial extracellular matrix (ECM). The ensuing penetration of the ECM is associated with the expr ession of ECM-degrading enzymes, such as endo-beta-D glucuronidase (he paranase), which cleaves heparan sulfate (HS) proteoglycans. We now re port that, depending on the local pH, a mammalian heparanase can funct ion either as an enzyme or as an adhesion molecule. At relatively acid ified pH conditions, heparanase performs as an enzyme, degrading HS. I n contrast, at the hydrogen ion concentration of a quiescent tissue, h eparanase binds specifically to HS molecules without degrading them, a nd thereby anchors CD4(+) human T lymphocytes. Thus, the local state o f a tissue can regulate the activities of heparanase and can determine whether the molecule will function as an enzyme or as a proadhesive m olecule.