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Published on: April 9, 2013
Immunoglobulin light chains modulate polymorphonuclear leucocyte apoptosis
G Cohen1, M Rudnicki, R Deicher
1Department of Medicine III, University of Vienna, Vienna, Austria. cohen@nephro.imed3.akh-wein.ac.at
Background:
Apoptosis of polymorphonuclear leucocytes (PMNLs) is important for the resolution of inflammation. Recently, we demonstrated that glucose-modified proteins increase PMNL apoptosis. No protein factors in sera of uraemic patients attenuating PMNL apoptosis have been identified to date.
Materials And Methods:
We tested the influence of commercially available monoclonal immunoglobulin light chains (IgLCs) from multiple myeloma patients and polyclonal IgLCs isolated from haemodialysis patients, previously shown to modulate PMNL functions and to contribute to their prestimulation, on PMNL apoptosis. We detected morphological changes, DNA strand breaks and the loss of DNA content.
Results:
All three apoptosis assays showed that kappa and lambda type IgLCs increase the percentage of viable PMNLs by inhibiting apoptosis in a concentration-dependent manner. The effect of IgLCs was abolished by specific antibodies. Addition of genistein abolished the reduction of PMNL apoptosis by IgLCs, suggesting that IgLCs exert their effect via tyrosine phosphorylation. Furthermore, we showed that the inhibition of caspase-3 activity is involved in the decrease of PMNL apoptosis.
Conclusion:
In concentrations present in sera of uraemic patients IgLCs could interfere with the normal resolution of inflammation and thereby contribute to the chronic inflammatory state found in end-stage renal disease patients.
Insights
Immunoglobulin light chains (IgLCs) in uremic patients inhibit polymorphonuclear leucocyte (PMNL) apoptosis. This finding suggests IgLCs may hinder inflammation resolution and contribute to chronic inflammation in end-stage renal disease.
Area of Science:
- Immunology
- Cell Biology
- Renal Medicine
Background:
- Polymorphonuclear leucocyte (PMNL) apoptosis is crucial for resolving inflammation.
- Previous research showed glucose-modified proteins enhance PMNL apoptosis.
- No serum factors in uremic patients inhibiting PMNL apoptosis were previously identified.
Purpose of the Study:
- To investigate the effect of immunoglobulin light chains (IgLCs) on PMNL apoptosis.
- To determine if IgLCs found in uremic patients' sera influence PMNL apoptosis.
Main Methods:
- Tested monoclonal and polyclonal IgLCs on PMNL apoptosis.
- Assessed morphological changes, DNA strand breaks, and DNA content loss.
- Investigated the role of tyrosine phosphorylation and caspase-3 inhibition.
Main Results:
- Both kappa and lambda IgLCs inhibited PMNL apoptosis in a concentration-dependent manner.
- IgLCs' effect was blocked by specific antibodies and genistein, indicating tyrosine phosphorylation involvement.
- Inhibition of caspase-3 activity was linked to reduced PMNL apoptosis.
Conclusions:
- IgLCs present in uremic patient sera can inhibit PMNL apoptosis.
- This inhibition may disrupt normal inflammation resolution.
- IgLCs could contribute to the chronic inflammatory state in end-stage renal disease.
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