Toxaphene, but not beryllium, induces human neutrophil chemotaxis and apoptosis via reactive oxygen species (ROS): involvement of caspases and ROS in the degradation of cytoskeletal proteins.
Chemicals of environmental concern are known to alter the immune system. Recent data indicate that some contaminants possess proinflammatory properties by activating neutrophils, an area of research that is still poorly investigated. We have previously documented that toxaphene activates human neutrophils to produce reactive oxygen species (ROS) and accelerates apoptosis by a yet unknown mechanism. In this study, we found that toxaphene induces another neutrophil function, chemotaxis. Furthermore, we found that toxaphene induces both chemotaxis and apoptosis via a ROS-dependent mechanism, since these responses were blocked by the addition of catalase to the culture. In addition, toxaphene was found to induce the degradation of the cytoskeletal proteins gelsolin, paxillin, and vimentin during apoptosis, and this was reversed by the addition of z-VAD-FMK (caspase inhibitor) or catalase, demonstrating the importance of caspases and ROS in this process. In contrast to toxaphene, we found that beryllium does not induce superoxide production, and, this correlates with its inability to induce chemotaxis and apoptosis. We conclude that toxaphene induces chemotaxis and apoptosis via ROS and that caspases and ROS are involved in the degradation of cytoskeletal proteins.
Lavastre
Valérie
V
INRS-Institut Armand-Frappier/Santé Humaine, Université du Québec, Pointe-Claire, Québec, Canada.
Roberge
Charles J
CJ
Pelletier
Martin
M
Gauthier
Marc
M
Girard
Denis
D
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis; D001608:Beryllium / Q000494:pharmacology*; D061945:Caspase Inhibitors; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005609:Free Radicals; D018260:Gelsolin / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D028321:Plant Preparations; D010940:Plant Proteins; D017382:Reactive Oxygen Species / Q000378:metabolism*; D054790:Ribosome Inactivating Proteins, Type 2; D013481:Superoxides / Q000378:metabolism; D014112:Toxaphene / Q000494:pharmacology*; D014118:Toxins, Biological / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D003598:Cytoskeletal Proteins; D005609:Free Radicals; D018260:Gelsolin; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D028321:Plant Preparations; D010940:Plant Proteins; D017382:Reactive Oxygen Species; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; D014746:Vimentin; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C009674:ribosome inactivating protein, Viscum; D013481:Superoxides; D014112:Toxaphene; D001608:Beryllium