Identification of the hyaluronan receptor for endocytosis (HARE)

Rat liver sinusoidal endothelial cells (LECs) express two hyaluronan (HA) r eceptors, of 175 and 300 kDa, responsible for the endocytic clearance of HA . We have characterized eight monoclonal antibodies (mAbs) raised against t he 175-kDa HA receptor partially purified from rat LECs. These mAbs also cr oss-react with the 300-kDa HA receptor. The 175-kDa HA receptor is a single protein, whereas the 300-kDa species contains three subunits, alpha, beta, and gamma at 260, 230, and 97 kDa, respectively (Zhou, B., Oka, J. A., and Weigel, P. H. (1999) J. Biol. Chem. 274, 35831-53834). The 97-kDa subunit was not recognized by any of the mAbs in Western blots. Based on their cros s-reactivity with these mAbs, the 175-, 230-, and 260-kDa proteins appear t o be related. Two of the mAbs inhibit I-125-HA binding and endocytosis by L ECs at 37 degreesC. All of these results confirm that the mAbs recognize th e bone fide LEC HA receptor. Indirect immunofluoresence shows high protein expression in liver sinusoids, the venous sinuses of the red pulp in spleen , and the medullary sinuses of lymph nodes. Because the tissue distribution for this endocytic HA receptor is not unique to liver, we propose the name HARE (HA receptor for endocytosis).