IgA induced activation of human mesangial cells: Independent of FcαR1 (CD 89)
| Autor: | Carlton R. Caflisch, Dianne K. Hammond, Janet A. Oka, Paul H. Weigel, Steven C. Diven, Randall M. Goldblum |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Cell mesangium Receptors Fc proto-oncogenes Biology polymeric IgA1 Monoclonal antibody Flow cytometry 03 medical and health sciences 0302 clinical medicine Genes jun Antigen Antigens CD Internal medicine medicine Humans Receptor Cells Cultured 030304 developmental biology 0303 health sciences Mesangial cell medicine.diagnostic_test Fc receptors Glomerulonephritis IGA IgA nephropathy Molecular biology Glomerular Mesangium Immunoglobulin A Endocrinology medicine.anatomical_structure Nephrology Cell culture Mesangium human mesangial cell glomerulonephritis 030215 immunology |
| Zdroj: | Kidney International. 54:837-847 |
| ISSN: | 0085-2538 |
| Popis: | IgA induced activation of human mesangial cells: Independent of Fc α R1 (CD 89). Background IgA nephropathy (IgAN) is characterized by deposition of polymers of IgA 1 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 IgA 1 to bind human mesangial cells (HMC). Activation of HMC by monomeric (mIgA 1 ) and heat aggregated IgA 1 (AIgA 1 ) was compared by Northern analysis of c- jun expression. The expression of Fc α R1 (CD89) mRNA on our cultured mesangial cells was also assessed by Northern analysis, reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. Results 125 I-mIgA 1 and 125 I-AIgA 1 bound to HMC in a dose-dependent, saturable manner with similar affinities. There were 1.2 × 10 6 binding sites per cell, with an affinity constant of 2.3 × 10 6 m -1 . AIgA 1 induced c- jun expression in a time and dose-dependent manner (2.4-fold above baseline after 60min exposure to AIgA 1 200 μ g/ml) while mIgA 1 had no effect on c- jun expression. No message for CD 89 was detectable in quiescent or AIgA 1 stimulated HMC by Northern analysis or RT-PCR using several primer sequences based on the sequence of U937 Fc α R cDNA. Flow cytometry on the mesangial cells, using My 43, a monoclonal antibody to Fc α R1 confirmed that CD 89 was not present on the cell. Conclusion These results demonstrate that HMC bind mIgA 1 and AIgA 1 with similar affinity. However, activation of HMC requires an aggregated form of IgA 1 . These processes are independent of Fc α R1, suggesting the presence of a new IgA receptor on mesangial cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|