Nephrology Dialysis Transplantation, Vol 14, Issue 5 1117-1123, Copyright © 1999 by Oxford University Press
Y Suzuki, C Ra, K Saito, S Horikoshi, S Hasegawa, T Tsuge, K Okumura and Y Tomino
Background. Most intensive investigations on the
pathogenesis of IgA nephropathy have focused on the process before IgA
deposition and the characteristics of IgA/IgA immune complex (IgA IC), but
it still remains uncertain whether mesangial IgA ICs may cause glomerular
injuries directly or are only secondary events of another pathological
process. To assess the role of IgA ICs in IgA nephropathy, we investigated
the characteristics of Fc&agr; receptor (Fc&agr;R) and FcR
&ggr; chain which is a signalling subunit of FcR in human mesangial
cells (MCs). Methods. Gene expression of Fc&agr;R
and FcR &ggr; chain of human cultured MCs was examined by RT-PCR and
subsequent Southern blot analyses. Sequence analyses after subcloning were
also performed for further confirmation. Expression of Fc&agr;R and FcR
&ggr; chain at the protein level and their physical association in MCs
were determined by immunoprecipitation after stimulation of the cells with
heat-aggregated IgA. Results. Two distinct cDNA
products were amplified from each cultured MC line. The sequence of the
major product of ∼900 bp was completely identical to that of
Fc&agr;R previously described. The smaller product had a 288 bp
deletion which corresponded to exon 2 encoding the extracellular domain 2
of Fc&agr;R. Gene expression of FcR &ggr; chain was also confirmed.
Furthermore, we proved the physical association of Fc&agr;R with the
FcR &ggr; chain by co-immunoprecipitation under stimulation with a high
dose of the heat-aggregated IgA. Conclusion. These
findings suggested that polymeric IgA and/or IgA IC can directly activate
MCs via Fc&agr;R associated with the &ggr; chain. Our data also
indicated that phenotypic variations of Fc&agr;R occur on MC, such as
splicing forms, the &ggr; chain association and/or the &agr; chain
expression itself, which may contribute to the pathogenesis of IgA
nephropathy. Keywords: Fc&agr;R; FcR &ggr;
chain; IgA nephropathy; mesangial cells; physical association
ORIGINAL ARTICLES
Expression and physical association of Fc&agr; receptor and Fc receptor &ggr; chain in human mesangial cells
Division of Nephrology, Department of Medicine and Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113, Japan; Corresponding author
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