Carbohydrate specificity of the galactose-recognizing receptor of rat peritoneal macrophages.
The galactose-recognizing system of rat peritoneal macrophages mediates the binding and uptake of desialylated blood cells and glycoproteins. To characterize the specificity of this receptor, binding studies were performed with various galactose derivatives as competitive inhibitors and sialidase-treated erythrocytes or asialoorosomucoid as ligands for receptors, which were either membrane-bound or isolated after solubilization. From the results obtained it can be concluded that galactose is recognized via its hydrophobic and/or hydrophilic regions, formed by the accumulation of OH-functions on one side and of H-atoms on the other ("side effect"), whereas the binding partner or the anomeric configuration of galactose has no significant influence. Although it became apparent that not a single hydroxyl group of the sugar is responsible for binding, the hydroxyl at C-4 seems to be most important, followed by the OH-group at C-3. Those at C-1, C-2 and C-6 do not play a great role. This order of importance ("position effect") was found with galactose, derivatized by methylation or otherwise, and with diastereomers of galactose. Whereas the recognition of a single galactose residue leads to weak binding only, an appropriate arrangement of several of these ligands in one molecule results in an enormous increase in the binding strength of each galactose residue. This "cluster effect" was observed not only with membrane-bound but also with solubilized receptor. However, the binding of asialoorosomucoid by the latter was better inhibited with free galactose, when compared with the membrane-bound receptor.
Lee
H
H
Biochemisches Institut der Universität zu Kiel.
Kelm
S
S
Yoshino
T
T
Schauer
R
R
D000818:Animals; D001212:Asialoglycoproteins; D002236:Carbohydrate Conformation; D002241:Carbohydrates / Q000494:pharmacology; D005260:Female; D005697:Galactosides / Q000378:metabolism*; D006027:Glycosides / Q000378:metabolism*; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D009844:Oligosaccharides / Q000494:pharmacology; D009961:Orosomucoid / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D001212:Asialoglycoproteins; D002241:Carbohydrates; D005697:Galactosides; D006027:Glycosides; D009844:Oligosaccharides; D009961:Orosomucoid; D011956:Receptors, Cell Surface; C017030:asialoorosomucoid; C039707:galactose receptor