Human polyspecific immunoglobulin for therapeutic use induces p21/WAF-1 and Bcl-2, which may be responsible for G1 arrest and long-term survival.
High-dose intravenous immunoglobulin (IVIg) is used as therapy in an increasing number of immune mediated disorders including infections and autoimmune conditions. IVIg exerts profound effects both in vivo as well as in vitro on humoral and cell-mediated immunity. In this study we investigated whether IVIg could alter the pattern of apoptosis and apoptosis related proteins including Bcl-2, Bax, p53, CD95, and p21/WAF-1, a protein well known to arrest cells in G1 phase of the cell cycle and finally proliferation marker Ki-67 on peripheral blood mononuclear cells (PBMC). The cells were cultured either unstimulated or with mitogen in the presence or absence of different IVIg preparations. A dual effect by IVIg was found. The incidence of apoptosis was elevated in activated Ki-67 and CD95 positive PBMC, whereas it was lower in small, nonactivated cells. The cells that survived were associated with a striking increase in the expression of p21/WAF-1 suggesting G1 arrest. A concomitant upregulation of Bcl-2 was also obtained by IVIg exposition resulting in long-term survival. We suggest that these abilities of IVIg to alter cell cycle progression and apoptosis could explain some of the beneficial effects obtained in vivo with IVIg therapy.
Department of Immunology, the Wenner-Gren Institute, Stockholm University, Stockholm, Sweden. carolineekberg@hotmail.com
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Ekberg
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Nordström
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Skansén-Saphir
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Mansouri
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Raqib
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Sundqvist
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Fernàndez
D000328:Adult; D000918:Antibody Specificity / Q000276:immunology*; D017209:Apoptosis; D001399:Azure Stains; D002455:Cell Division; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000502:physiology*; D016193:G1 Phase; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology* / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008213:Lymphocyte Activation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000502:physiology*; D013997:Time Factors
D001399:Azure Stains; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016756:Immunoglobulins, Intravenous; D019253:Proto-Oncogene Proteins c-bcl-2