IgA induced activation of human mesangial cells: independent of FcalphaR1 (CD 89).
BACKGROUND
IgA nephropathy (IgAN) is characterized by deposition of polymers of IgA1 in the mesangium, accumulation of mesangial matrix and mesangial cell proliferation. Activation of the mesangial cell by IgA, via an IgA receptor, may be an initiating event in the pathology of IgAN.


METHODS
We examined the ability of radiolabeled, normal serum IgA1 to bind human mesangial cells (HMC). Activation of HMC by monomeric (mIgA1) and heat aggregated IgA1 (AIgA1) was compared by Northern analysis of c-jun expression. The expression of FcalphaR1 (CD89) mRNA on our cultured mesangial cells was also assessed by Northern analysis, reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry.


RESULTS
125I-mIgA1 and 125I-AIgA1 bound to HMC in a dose-dependent, saturable manner with similar affinities. There were 1.2 x 10(6) binding sites per cell, with an affinity constant of 2.3 x 10(6) M(-1). AIgA1 induced c-jun expression in a time and dose-dependent manner (2.4-fold above baseline after 60 min exposure to AIgA1 200 microg/ml) while mIgA1 had no effect on c-jun expression. No message for CD 89 was detectable in quiescent or AIgA1 stimulated HMC by Northern analysis or RT-PCR using several primer sequences based on the sequence of U937 FcalphaR cDNA. Flow cytometry on the mesangial cells, using My 43, a monoclonal antibody to FcalphaR1 confirmed that CD 89 was not present on the cell.


CONCLUSIONS
These results demonstrate that HMC bind mIgA1 and AIgA1 with similar affinity. However, activation of HMC requires an aggregated form of IgA1. These processes are independent of FcalphaR1, suggesting the presence of a new IgA receptor on mesangial cells.
Diven
S C
SC
Department of Pediatrics, University of Texas Medical Branch, Galveston 77555-0373, USA. Sdiven@UTMB.edu
Caflisch
C R
CR
Hammond
D K
DK
Weigel
P H
PH
Oka
J A
JA
Goldblum
R M
RM
D015703:Antigens, CD / Q000032:analysis / Q000502:physiology*; D002478:Cells, Cultured; D016758:Genes, jun; D005920:Glomerular Mesangium / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000209:etiology; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism / Q000494:pharmacology*; D011961:Receptors, Fc / Q000032:analysis / Q000502:physiology*
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc