IgA induced activation of human mesangial cells: Independent of FcαR1 (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 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.