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Published on: August 10, 2015
Enrichment and characterization of dendritic cells from rat renal mesangium
R Gieseler1, P R Hoffmann, R Kuhn
1Department of Immunology, Georg-August University, Göttingen, Germany.
Insights
Kidney mesangial cells are potent immune responders, similar to splenic dendritic cells (DC). These kidney dendritic cells (DC) initiate immune reactions and may play a role in transplant rejection and glomerulonephritis.
Area of Science:
- Immunology
- Nephrology
Background:
- Dendritic cells (DC) initiate immune responses and are found in most tissues.
- The kidney's glomerular mesangium is hypothesized to harbor the most potent DC population.
- Understanding kidney dendritic cells (DC) is crucial for immune-related kidney diseases.
Purpose of the Study:
- To enrich and characterize dendritic cells (DC) residing in the rat kidney's glomerular mesangium.
- To investigate the phenotype and function of these mesangial dendritic cells (DC).
- To assess the potential role of mesangial dendritic cells (DC) in kidney diseases and transplant rejection.
Main Methods:
- Enrichment and characterization of low-density cells from rat kidney glomeruli.
- Immunophenotyping using monoclonal antibodies (OX-6, OX-42, ED1, OX-62, ED2, R3) and enzyme histochemistry.
- Functional assays including allogeneic mixed leukocyte reaction and phagocytosis of opsonized E. coli.
Main Results:
- Mesangial dendritic cells (DC) exhibited distinct morphological and phenotypic characteristics.
- A significant subset (60%) of mesangial dendritic cells (DC) expressed antigen recognized by the R3 antibody.
- Mesangial dendritic cells (DC) demonstrated potent allostimulatory activity, comparable to splenic dendritic cells (DC), but lacked phagocytic capacity.
Conclusions:
- Kidney mesangial dendritic cells (DC) are phenotypically and functionally similar to splenic dendritic cells (DC).
- These cells likely represent different maturation-dependent subsets, with OX-62 expression indicating maturity.
- Mesangial dendritic cells (DC) are proposed to be involved in immune responses within the kidney, including allograft rejection and glomerulonephritis.
Abstract:
Dendritic cells (DC) initiate primary immune reactions and are distributed throughout most tissues. The most potent DC population of the kidney has long been suggested to reside within the glomerular mesangium. Using LEW.1A rats, we enriched and characterized such low-density cells. Mesangial DC generally exhibited round to oval cell bodies and cytoplasmic veils. Phenotypically, these cells were 100% OX-6++, 45% OX-42++, 35% ED1low, 10% OX-62low, and negative for ED2 and alpha-naphtylbutyrate esterase. Introducing a new monoclonal antibody, R3, which stains a subset of splenic DC, we showed strong antigen expression on 60% of mesangial DC. Correlating cell populations were detected immunohistochemically. Functionally, mesangial DC potently stimulated allogeneic mixed leucocyte reactions, but did not phagocytose opsonized Escherichia coli. In addition to their striking phenotypic similarity with autologous splenic DC, mesangial DC exhibited 88% of the allostimulatory activity of splenic DC. Calculation indicated approximately two mesangial DC per glomerulum. We suggest that these cells comprise different maturation-dependent subsets. The OX-62 integrin especially appears to be expressed only on mature mesangial DC, which may correlate to lymphoid veiled cells or interdigitating DC. An employment of mesangial DC in experimental models of acute allograft rejection or glomerulonephritis is discussed.
