Mechanisms involved in methylmercuric chloride (MeHgCl)-induced suppression of human neutrophil apoptosis.
We have previously demonstrated that concentrations of 1-10 microM of methylmercuric chloride (MeHgCl) that are cytotoxic to monocytes-macrophages can curiously inhibit neutrophil apoptosis by a yet unknown mechanism. In the present study, we demonstrate that, as with the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), a classical inhibitor of neutrophil apoptosis, treatment of cells with 5 microM MeHgCl induces de novo protein synthesis and prevents the loss of expression of the antiapoptotic Mcl-1 protein. The expression of the cytoskeletal proteins gelsolin, paxillin and vinculin was similar in MeHgCl- or GM-CSF-induced suppression of apoptosis. However, MeHgCl prevents the degradation of vimentin differently than GM-CSF. Apoptosis was further confirmed by flow cytometry (FITC annexin-V), and by monitoring CD16 cell surface expression. Curiously, unlike GM-CSF, MeHgCl did not prevent CD16 shedding. We conclude that, like GM-CSF, MeHgCl can delay neutrophil apoptosis by inducing de novo protein synthesis and by preventing the loss of the antiapoptotic Mcl-1 protein. However, unlike GM-CSF, MeHgCl induces an atypical degradation of vimentin without preventing CD16 shedding.
Moisan
Eliane
E
INRS-Institut Armand-Frappier, Université du Québec, 245 boulevard Hymus, Pointe-Claire, PQ, Canada.
Kouassi
Edouard
E
Girard
Denis
D
D017209:Apoptosis / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018260:Gelsolin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism / Q000494:pharmacology; D008767:Methylmercury Compounds / Q000378:metabolism / Q000494:pharmacology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D051419:Paxillin; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2; D017452:Receptors, IgG / Q000378:metabolism; D013462:Sulfur Radioisotopes / Q000378:metabolism; D014746:Vimentin / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D016596:Vinculin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology
D003598:Cytoskeletal Proteins; D018260:Gelsolin; D015848:Interleukin-5; D008767:Methylmercury Compounds; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017452:Receptors, IgG; D013462:Sulfur Radioisotopes; D014746:Vimentin; D016596:Vinculin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C004925:methylmercuric chloride