IgA induced activation of human mesangial cells: Independent of FcαR1 (CD 89)

S. C. Diven, C. R. Caflisch, D. K. Hammond, P. H. Weigel, J. A. Oka, R. M. Goldblum

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

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 FcαR1 (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 106 binding sites per cell, with an affinity constant of 2.3 x 106 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 μg/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 FcαR cDNA. Flow cytometry on the mesangial cells, using My 43, a monoclonal antibody to FcαR1 confirmed that CD 89 was not present on the cell. Conclusion. 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 FcαR1, suggesting the presence of a new IgA receptor on mesangial cells.

Original languageEnglish (US)
Pages (from-to)837-847
Number of pages11
JournalKidney International
Volume54
Issue number3
DOIs
StatePublished - Jan 1 1998

Keywords

  • Fc receptors
  • Glomerulonephritis
  • Human mesangial cell
  • IgA nephropathy
  • Mesangium
  • Polymeric IgA
  • Proto-oncogenes

ASJC Scopus subject areas

  • Nephrology

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    Diven, S. C., Caflisch, C. R., Hammond, D. K., Weigel, P. H., Oka, J. A., & Goldblum, R. M. (1998). IgA induced activation of human mesangial cells: Independent of FcαR1 (CD 89). Kidney International, 54(3), 837-847. https://doi.org/10.1046/j.1523-1755.1998.00054.x