Identification of a novel Fcalpha receptor expressed by human mesangial cells.
BACKGROUND
IgA nephropathy (IgAN) is characterized by mesangial deposits of polymeric IgA (pIgA). The pathological consequences of IgA deposition are believed to center on direct interaction between IgA and the glomerular mesangial cell (MC). We have characterized a novel mesangial receptor that recognizes the Fc portion of IgA.


METHODS
Five primary MC cultures were evaluated for IgA binding by flow cytometry, and specificity of binding was determined by competitive inhibition. Relative affinities of the receptor for all IgA isoforms were also determined, and binding of pIgA1 was compared to monomer. The identified Fc receptor was then compared with CD89, hitherto the only other Fcalpha receptor reported. CD89 protein and mRNA expression were detected by conventional and intracellular flow cytometry, sequencing of reverse transcription-polymerase chain reaction (RT-PCR) products, and Northern blotting.


RESULTS
All MCs constitutively expressed a receptor that bound IgA in an Fcalpha-dependent fashion. The receptor recognized secretory and serum IgA1 and IgA2 equally, but pIgA bound with much greater affinity than monomer. At no time were we able to detect CD89 synthesis, although three novel CD89-related mRNA transcripts were identified by RT-PCR.


CONCLUSIONS
We have clearly demonstrated that MCs consistently express an FcalphaR distinct from the myeloid FcalphaR CD89. This novel receptor binds pIgA with high affinity and may therefore mediate the mesangial injury that follows IgA deposition in IgAN. While immunogenically distinct, the mesangial Fcalpha receptor may share some molecular homology with CD89, as mRNA transcripts with partial identity to CD89 were found in all five MC cultures.
Barratt
J
J
Department of Nephrology, Leicester General Hospital, Leicester, England, United Kingdom. JBarr20401@aol.com
Greer
M R
MR
Pawluczyk
I Z
IZ
Allen
A C
AC
Bailey
E M
EM
Buck
K S
KS
Feehally
J
J
D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D015152:Blotting, Northern; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000737:chemistry*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011961:Receptors, Fc / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015703:Antigens, CD; C036832:Fc(alpha) receptor; C045281:IgA receptor; D007070:Immunoglobulin A; D012333:RNA, Messenger; D011961:Receptors, Fc