TY - JOUR
T1 - Up-regulation of the iC3b receptor (CR3) is neither necessary nor sufficient to promote neutrophil aggregation
AU - Philips, M. R.
AU - Buyon, J. P.
AU - Winchester, R.
AU - Weissmann, G.
AU - Abramson, S. B.
PY - 1988
Y1 - 1988
N2 - 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°C and rewarmed to 37°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 salicylkate inhibited aggregation 55 ± 4%, but had no effect on CR3 up-regulation. Conversely, 1 mM tetracaine complewtely 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.
AB - 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°C and rewarmed to 37°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 salicylkate inhibited aggregation 55 ± 4%, but had no effect on CR3 up-regulation. Conversely, 1 mM tetracaine complewtely 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.
UR - http://www.scopus.com/inward/record.url?scp=0023783485&partnerID=8YFLogxK
U2 - 10.1172/JCI113623
DO - 10.1172/JCI113623
M3 - Article
C2 - 2841354
AN - SCOPUS:0023783485
SN - 0021-9738
VL - 82
SP - 495
EP - 501
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 2
ER -