title: Up-regulation of the iC3b receptor (CR3) is neither necessary nor sufficient to promote neutrophil aggregation.
abstract: The iC3b receptor (CR3) is required for neutrophil adhesive functions, including homotypic aggregation. Because stimuli that enhance neutrophil adhesion also induce up-regulation of surface CR3, it is widely held that these two responses are causally related. We have dissociated CR3 display (immunofluorescence) from CR3 function (aggregation). Neutrophils isolated at 4 degrees C and rewarmed to 37 degrees C up-regulated surface CR3 twofold, but did not aggregate. The kinetics of FMLP-induced CR3 up-regulation were discordant with those of aggregation. In the absence of extracellular divalent cations, CR3 expression increased twofold after exposure to FMLP, but neutrophils did not aggregate. FMLP elicited 3.5-fold more aggregation than the ionophore A23187, yet less than one-half as much CR3 up-regulation. 3 mM sodium salicylate inhibited aggregation 55 +/- 4%, but had no effect on CR3 up-regulation. Conversely, 1 mM tetracaine completely inhibited CR3 up-regulation, while significantly enhancing aggregation. Neutroplasts expressed CR3, but did not up-regulate the receptor; in contrast, FMLP induced CR3-dependent aggregation of neutroplasts. We conclude that, although constitutive surface CR3 is required for neutrophil aggregation, the up-regulation of CR3 is neither necessary nor sufficient to promote cell-cell adhesion.
authors.affiliation: Department of Medicine, New York University Medical Center 10016.
authors.forename: M R
authors.initials: MR
authors.lastname: Philips
authors.forename: J P
authors.initials: JP
authors.lastname: Buyon
authors.forename: R
authors.initials: R
authors.lastname: Winchester
authors.forename: G
authors.initials: G
authors.lastname: Weissmann
authors.forename: S B
authors.initials: SB
authors.lastname: Abramson
mesh_terms: D000911:Antibodies, Monoclonal / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D002413:Cations, Divalent; D002449:Cell Aggregation / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D003176:Complement C3 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007700:Kinetics; D007975:Leukotriene B4 / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011951:Receptors, Complement / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D017463:Receptors, Complement 3b; D012980:Sodium Salicylate / Q000494:pharmacology; D013696:Temperature
chemical_list: D000911:Antibodies, Monoclonal; D002413:Cations, Divalent; D003176:Complement C3; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D007975:Leukotriene B4; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D012980:Sodium Salicylate