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

Abstract

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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