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Blood, 15 July 2006, Vol. 108, No. 2, pp. 584-590.
Prepublished online as a Blood First Edition Paper on March 21, 2006; DOI 10.1182/blood-2005-12-4997.
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Submitted December 19, 2005
Accepted March 8, 2006
Neutrophil responsiveness to IgG determined by fixed ratios of mRNA levels for activating and inhibitory Fc RII (CD32): stable over time and unaffected by cytokines
Edwin van Mirre*, Willemijn B Breunis, Judy Geissler, C E Hack, Martin de Boer, Dirk Roos, and Taco W Kuijpers
Department of Blood Cell Research, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; Department of Immunopathology, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Department of Blood Cell Research, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands
Department of Immunopathology, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; Department of Clinical Chemistry, VU Medical Center, Amsterdam, The Netherlands
Department of Blood Cell Research, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
* Corresponding author; email: e.vanmirre{at}sanquin.nl.
We tested the hypothesis that the ratio between the activating and inhibitory Fc receptor type 2 (FcRII) in neutrophils determines their responsiveness to immune complexes. We measured mRNA levels of FcRII isoforms and observed differences in the ratio of FcRIIa/FcRIIb2 mRNA in granulocytes of 50 Caucasian and 10 negroid healthy volunteers, and found four discrete groups of ratios, i.e. 4:1; 3:1, 2:1 or 1:1. The response to either dimeric IgG or aggregated IgG (aIgG) was assessed. Upregulation of CD11b on the surface as well as the elastase release was significantly more pronounced in neutrophils with a high FcRIIa/FcRIIb2 mRNA ratio of 4:1 as compared to 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 FcRIIa/FcRIIb2 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 FcRIIa/FcRIIb2 mRNA ratios of 2:1, 3:1 or 4:1.
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