Up-regulation of the iC3b receptor (CR3) is neither necessary nor sufficient to promote neutrophil aggregation.
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.
Philips
M R
MR
Department of Medicine, New York University Medical Center 10016.
Buyon
J P
JP
Winchester
R
R
Weissmann
G
G
Abramson
S B
SB
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
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