Wheat germ agglutinin inhibits the C5a receptor interaction: implications for receptor microheterogeneity and ligand binding site.
Wheat germ agglutinin (WGA) has been shown to inhibit the interaction of C5a with the C5a receptor on both polymorphonuclear neutrophils (PMNs) and the histiocytic cell line U937. The level of inhibition with isolated receptor preparations is 100%, and on intact cells 10 to 20% of the receptor population appear to retain their ability to bind C5a in the presence of WGA. In contrast, this lectin completely inhibits the C5a-mediated degranulation of PMN primary and secondary granules, suggesting that the population of C5a receptors responsible for mediating degranulation is also recognized by WGA. More than 50% of the receptors appear to be blocked before an effect on degranulation occurs. This inhibition by WGA does not appear to be due to down-regulation of C5a receptors from the cell surface, excessive aggregation of receptor sites, or interaction of WGA with the carbohydrate portion of the C5a molecule. The inhibition is reversed by N-acetylglucosamine but not by sialic acid. This effect appears to be specific for WGA because various other lectins do not inhibit the C5a receptor interaction. That the inhibition by WGA is due to direct binding of the lectin to N-acetylglucosamine residues on the C5a receptor is strongly supported by the ability of the cross-linked C5a-receptor complex to bind to and be specifically eluted from a WGA-Affigel affinity matrix. These observations are consistent with hypothesis that the population of C5a receptors on leukocytes exhibits microheterogeneity with respect to structure (carbohydrate content) and/or function.
Johnson
R J
RJ
Baxter Healthcare Corporation, Round Lake, IL 60073.
Simpson
S
S
Van Epps
D E
DE
Chenoweth
D E
DE
D001665:Binding Sites; D002846:Chromatography, Affinity; D015936:Complement C5a / Q000378:metabolism; D005434:Flow Cytometry; D006098:Granulocytes / Q000648:ultrastructure; D006801:Humans; D008024:Ligands; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D014909:Wheat Germ Agglutinins / Q000008:administration & dosage* / Q000378:metabolism
D008024:Ligands; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D014909:Wheat Germ Agglutinins; D015936:Complement C5a