Preparation and characterization of a derivative of wheat germ agglutinin which specifically inhibits polymorphonuclear leukocyte chemotaxis to the synthetic chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine.
A nonagglutinating derivative of wheat germ agglutinin (WGA), prepared by treating the native lectin with cyanogen bromide and formic acid and purified by affinity chromatography on an N-acetyl-D-glucosamine column, inhibited human polymorphonuclear leukocyte (PMN) chemotaxis to the synthetic chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). The WGA derivative (WGA-D) did not influence either the ability of PMN to migrate randomly or their chemotactic response to the complement-derived peptide C5a. Similarly, WGA-D had no effect on either FMLP-induced PMN polarization or other FMLP-induced PMN functions (i.e., selective discharge of lysosomal enzymes from cytochalasin B-treated cells, generation of superoxide anion). The inhibition of FMLP-induced PMN chemotaxis by WGA-D could not be reversed by washing the cells, or by incubating lectin-treated PMN at 37 degrees C for 20 min. The inhibitory effect of WGA-D was mediated by its specific binding to N-acetyl-D-glucosamine residues on the cell surface. WGA-D did not alter the specific binding of [3H]-FMLP to its receptor(s) on the PMN membrane. The data presented here suggest that WGA-D inhibits FMLP-induced PMN chemotaxis at a step distal to stimulus recognition.
D000328:Adult; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D037102:Lectins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D008247:Lysosomes / Q000201:enzymology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000032:analysis; D011975:Receptors, Mitogen / Q000032:analysis; D014909:Wheat Germ Agglutinins
D007166:Immunosuppressive Agents; D037102:Lectins; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D011975:Receptors, Mitogen; D014909:Wheat Germ Agglutinins; C027503:wheat germ agglutinin receptor; D009240:N-Formylmethionine Leucyl-Phenylalanine