Neutrophil responsiveness to IgG, as determined by fixed ratios of mRNA levels for activating and inhibitory FcgammaRII (CD32), is stable over time and unaffected by cytokines.
We tested the hypothesis that the ratio between the activating and inhibitory Fcgamma receptor type II (FcgammaRII) in neutrophils determines their responsiveness to immune complexes. We measured mRNA levels of FcgammaRII isoforms and observed differences in the ratio of FcgammaRIIa to FcgammaRIIb2 mRNA in granulocytes of 50 white and 10 black healthy volunteers, and found 4 discrete groups of ratios (ie, 4:1; 3:1, 2:1, or 1:1). The response to either dimeric IgG or aggregated IgG (aIgG) was assessed. Up-regulation of CD11b on the surface as well as the elastase release was significantly more pronounced in neutrophils with a high FcgammaRIIa/FcgammaRIIb2 mRNA ratio of 4:1 compared with a 2:1 or 1:1 ratio. Individual ratios as well as the functional responsiveness of neutrophils were constant over time, as was tested over 12 months. Neutrophil stimulation with various agents in vitro did not alter the FcgammaRIIa/FcgammaRIIb2 mRNA ratio in the neutrophils of these donors, in clear contrast to the findings in their mononuclear cells. We found a strong association between the 2B.4 haplotype of the FCGR2B promoter with increased transcriptional activity in individuals with 1:1 ratios and the more common low-expression 2B.1 haplotype in individuals with FcgammaRIIa/FcgammaRIIb2 mRNA ratios of 2:1, 3:1, or 4:1.
Department of Blood Cell Research, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, The Netherlands. e.vanmirre@sanquin.nl
Edwin
E
van Mirre
Willemijn B
WB
Breunis
Judy
J
Geissler
C Erik
CE
Hack
Martin
M
de Boer
Dirk
D
Roos
Taco W
TW
Kuijpers
D000293:Adolescent; D000328:Adult; D044383:Black People / Q000235:genetics; D039481:CD11b Antigen / Q000235:genetics; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D019272:Leukocyte Elastase; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis* / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation; D044465:White People / Q000235:genetics
D039481:CD11b Antigen; D016207:Cytokines; D007074:Immunoglobulin G; D020033:Protein Isoforms; D012333:RNA, Messenger; D017452:Receptors, IgG; D019272:Leukocyte Elastase