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Published on: August 19, 2020
Human glomerular mesangial cells express CD16 and may be stimulated via this receptor
M Morcos1, G M Hänsch, M Schönermark
1Institute of Immunology and Serology, Medical Faculty of Mannheim, University of Heidelberg, Germany.
Insights
Human glomerular mesangial cells (GMC) express CD16, a receptor for IgG. This receptor may play a role in kidney inflammation by mediating interleukin-6 release upon immune complex binding.
Area of Science:
- Immunology
- Nephrology
- Cell Biology
Background:
- CD16 is a low-affinity IgG receptor found on various immune cells.
- Glomerular mesangial cells (GMCs) are crucial for kidney function and filtration.
- The presence and function of CD16 in GMCs are not well-understood.
Purpose of the Study:
- To investigate the expression and characterization of CD16 on human glomerular mesangial cells (GMCs).
- To determine the functional role of CD16 in GMCs, particularly in response to immune complexes.
- To explore the potential involvement of GMC CD16 in inflammatory kidney diseases.
Main Methods:
- Western blot analysis, cell ELISA, and in situ hybridization to detect CD16 expression.
- Reverse polymerase chain reaction (RT-PCR) and sequence analysis for molecular characterization.
- Stimulation assays with aggregated gammaglobulin and monoclonal antibodies to CD16.
- Measurement of interleukin-6 release as a functional readout.
Main Results:
- CD16 was detected on cultured human GMCs using multiple methods.
- Sequence analysis indicated that GMC-CD16 is the transmembrane form, similar to NK-CD16.
- CD16 expression levels did not change upon stimulation with aggregated gammaglobulin.
- Incubation with aggregated gammaglobulin or anti-CD16 antibodies induced a dose- and time-dependent release of interleukin-6 from GMCs.
Conclusions:
- Human GMCs express the transmembrane form of CD16.
- CD16 signaling in GMCs can trigger the release of the pro-inflammatory cytokine interleukin-6.
- CD16-mediated immune complex recognition by GMCs may contribute to the pathogenesis of glomerulonephritis.
Abstract:
CD16, a low affinity receptor for IgG, was found on cultured human glomerular mesangial cells (GMC) by Western blot analysis, cell ELISA and in situ hybridization. To characterize the molecule in more detail, reverse polymerase chain reaction was performed and the PCR products were analyzed. From sequence analysis and from hybridization experiments with oligonucleotides specific for either the transmembrane form or the glycosylphosphatidylinositol anchored form it was found that GMC-CD16 was similar to NK-CD16. This indicates that GMC express the transmembrane form of CD16. Comparison between nonstimulated GMC and GMC stimulated by aggregated gammaglobulin revealed no qualitative or quantitative difference in the expression of CD16. Incubation of GMC with aggregated gammaglobulin or with monoclonal antibodies to CD16 was followed by a time and dose dependent release of interleukin-6, suggesting that signals were transmitted by CD16. The occupancy of CD16 by immune complexes that may be deposited in various forms of glomerulonephritis might contribute to the perpetuation of inflammatory processes in the kidney.
