G Cohen1, M Rudnicki, R Deicher, W H Hörl. 1. Department of Medicine III, University of Vienna, Vienna, Austria. cohen@nephro.imed3.akh-wein.ac.at
Abstract
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.
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 myelomapatients 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 diseasepatients.