Relations between Fc receptor function and locomotion in human lymphocytes.
The relationship between the surface binding sites on human lymphocytes for chemotactic factors and for the Fc fraction of IgG was investigated using both blood lymphocytes and established cultures of human lymphoblasts. Pretreatment of human blood lymphocytes with a variety of chemotactic factors inhibited Fc-rosette formation. This was true even of small formylated peptides, for example, formyl-methionyl-phenylalanine (chemotactic) inhibited Fc-rosetting but unformylated methionyl-phenylalanine (non-chemotactic) did not. Conversely pretreatment of lymphocytes with IgG inhibited their locomotor reactions to a variety of chemoattractants. Aggregated IgG was more inhibitory than non-aggregated IgG and the inhibition was mediated via the Fc piece. In a filter assay, native IgG was chemokinetic but not chemotactic for lymphocytes. Heat-aggregated IgG induced more locomotion of lymphocytes than native IgG, and was possibly chemotactic, but no unequivocally so. The possibility that chemotactic factors and the Fc portion of IgG compete for the same cell surface receptor was investigated by binding studies using cultured lymphoblasts. These studies suggested that the reciprocal inhibition could not be explained by competition for receptors. An alternative explanation was suggested by the finding that inhibition of locomotion by aggregated IgG was dependent on the presence of divalent cations at the time the IgG was added, and did not occur in the presence of the calcium ionophore A23187. Addition of aggregated IgG or chemotactic factors to lymphocytes thus may lead to a gated entry of calcium, and following closure of the calcium gate, the cells become relatively unresponsive to further stimulation.
D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D006801:Humans; D007074:Immunoglobulin G; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D010455:Peptides / Q000494:pharmacology; D011961:Receptors, Fc; D012397:Rosette Formation
D002630:Chemotactic Factors; D007074:Immunoglobulin G; D010455:Peptides; D011961:Receptors, Fc; D000001:Calcimycin; D002118:Calcium