The endocytic hyaluronan (HA) receptor of liver sinusoidal endothelial cells (LECs) is responsible for the clearance of HA and other glycosaminoglycans from the circulation in mammals. We report here for the first time the purification of this liver HA receptor. Using lectin and immuno-affinity chromatography, two HA receptor species were purified from detergent-solubilized membranes prepared from purified rat LECs. In nonreducing SDS-polyacrylamide gel electrophoresis (PAGE), these two proteins migrated at 175-and ϳ300 kDa corresponding to the two species previously identified by photoaffinity labeling of live cells as the HA receptor (Yannariello-Brown, J., Frost, S. J., and Weigel, P. H. (1992) J. Biol. Chem. 267, 20451-20456). These two proteins co-purify in a molar ratio of 2:1 (175:300), and both proteins are active, able to bind HA after SDS-PAGE, electrotransfer, and renaturation. After reduction, the 175-kDa protein migrates as a ϳ185-kDa protein and is not able to bind HA. The 300-kDa HA receptor is a complex of three disulfide-bonded subunits that migrate in reducing SDS-PAGE at ϳ260, 230, and 97 kDa. These proteins designated, respectively, the ␣, ␤, and ␥ subunits are present in a molar ratio of 1:1:1 and are also unable to bind HA when reduced. The 175-kDa protein and all three subunits of the 300-kDa species contain N-linked oligosaccharides, as indicated by increased migration in SDS-PAGE after treatment with N-glycosidase F. Both of the deglycosylated, nonreduced HA receptor proteins still bind HA.HA 1 is an important extracellular matrix component of all tissues and plays a key role in development, cell proliferation, cell adhesion, recognition, morphogenesis, differentiation, and inflammation (1-4). The daily total body turnover of HA in humans is at least 1 g/day (4). HA degradation and removal in the body occurs via two clearance systems (3): one is in the lymphatic system, which accounts for ϳ85% of the HA turnover, and another system is hepatic, accounting for ϳ15% of the total body HA turnover. HA in tissues throughout the body is continuously synthesized and degraded. Very large HA molecules (ϳ10 7 Da) are partially degraded to large fragments (ϳ10 6 Da) that are then released from the matrix and flow with the lymph to lymph nodes. The majority of HA (ϳ85%) is completely degraded in the lymph nodes by unknown mechanisms and the remaining HA (ϳ15%) that passes through the nodes finally enters the blood. Clearance of this circulating HA is presumably important for normal health (3, 4). Elevated serum HA levels are found in several disease conditions such as liver cirrhosis, rheumatoid arthritis, psoriasis, scleroderma, and some cancers (5-7).LECs have a very active recycling, endocytic receptor that removes HA and other glycosaminoglycans, such as chondroitin sulfate, from the circulation (3, 8 -10). Earlier reports misidentified this LEC HAR as ICAM-1 (11, 12), also known as CD54, which is a 90-kDa protein. This finding was later recognized as an artifact in that ICAM-1 bound nonspecifica...

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These results demonstrate that HMC bind mIgA1 and AIgA1 with similar affinity. However, activation of HMC requires an aggregated form of IgA1. These processes are independent of FcalphaR1, suggesting the presence of a new IgA receptor on mesangial cells.

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Abstract. Isolated rat hepatocytes bind to synthetic flat polyacrylamide matrices containing covalently attached galactose residues in a sugar-specific and concentration-dependent manner. Cell binding is mediated by the asialoglycoprotein receptor and occurs as a threshold response at or above a critical concentration of sugar in the matrix. Hepatocytes in the presence or absence of serum were able to spread on these synthetic galactose surfaces and were morphologically similar to cells on tissue culture plastic. Cell spreading also occurred as a threshold response but at a much higher critical concentration of sugar than for the cellbinding response. Above the critical concentration for spreading, the area occupied by a cell increased as the sugar concentration increased. By manipulating the galactose content of the matrix, cell spreading and cell binding can be differentiated as independent and separable threshold responses to the extracellular substratum.