The hyaluronan receptor for endocytosis (HARE) is not CD44 or CD54 (ICAM-1).
Mammalian liver contains an endocytic, recycling receptor that mediates the clearance of hyaluronan (HA) and chondroitin sulfate from the circulation. McCourt et al. [J. Biol. Chem. 269 (1994) 30081] previously reported that this endocytic liver HA receptor was ICAM-1. In contrast, we purified this HA receptor for endocytosis (HARE) from rat liver sinusoidal endothelial cells (LECs) and obtained two novel large proteins [Zhou et al., J. Biol. Chem. 274 (1999) 33831]. The goal of the present study was to clarify this inconsistency and determine whether CD44, which is also an HA receptor, or ICAM-1 (CD54) is identical to, or is part of, HARE. Although isolated liver LECs contain HARE, CD44, and ICAM-1, confocal fluorescence microscopy showed that the two latter proteins have cellular distributions that are distinct from and essentially nonoverlapping with HARE. HA accumulation by cultured LECs was inhibited >98% by an antibody against HARE and unaffected by antibodies to ICAM-1 or CD44, indicating that virtually all specific HA uptake is mediated by HARE and not by ICAM-1 or CD44. Finally, no reactivity was observed against purified HARE in an ELISA-based assay using CD44 or ICAM-1 antibodies. The results confirm that the mammalian endocytic HA receptor is HARE and is not ICAM-1 or CD44.
Weigel
Janet A
JA
Department of Biochemistry and Molecular Biology, The Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Raymond
Robert C
RC
Weigel
Paul H
PH
D000818:Animals; D002478:Cells, Cultured; D004705:Endocytosis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018960:Hyaluronan Receptors / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism; D018613:Microscopy, Confocal; D051381:Rats
D018960:Hyaluronan Receptors; D018799:Intercellular Adhesion Molecule-1; D008358:Mannose