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(Journal of Leukocyte Biology. 2001;70:367-373.)
© 2001 by Society for Leukocyte Biology

Activation of human neutrophils in vitro and dieldrin-induced neutrophilic inflammation in vivo

Martin Pelletier^*, Charles J. Roberge, Marc Gauthier^*, Karen Vandal, Philippe A. Tessier and Denis Girard^*

^* INRS-Institut, Armand-Frappier/Santé Humaine, Université du Québec, Pointe-Claire;
Association du Cancer de l’Est du Québec, Rimouski; and
Centre de Recherche en Infectiologie, Université Laval, Sainte-Foy, Québec, Canada

Correspondence: Denis Girard, Ph.D., INRS-Institut Armand-Frappier/Santé Humaine, 245 boul Hymus, Pointe-Claire, Québec H9R 1G6, Canada. E mail: Denis.Girard@INRS-Sante.Uquebec.ca

Many chemicals of environmental concern are known to alter the immune system and are considered toxic molecules because they affect immune cell functions. Inflammation related to environmental chemical exposure, however, is poorly documented, except that from air pollutants. In this study, we found that the organochlorine insecticide dieldrin could not alter the ability of human neutrophils to phagocytose opsonized sheep red blood cells at nonnecrotic concentrations (0.1, 1, 10, and 50 µM). However, dieldrin was found to increase human neutrophil superoxide production, RNA synthesis, and proinflammatory cytokine interleukin-8 production. The normal apoptotic rate of neutrophils evaluated by both cytology and flow cytometry (CD-16 staining) was not altered by dieldrin treatments, and this was correlated with its inability to inhibit spreading of neutrophils onto glass. Using the murine air pouch model, we found that dieldrin induces a neutrophilic inflammation. Taken together, these results demonstrated that dieldrin is a proinflammatory contaminant. To our knowledge, this is the first report establishing that dieldrin is a contaminant exhibiting proinflammatory properties. In addition, it is the first time that the murine air pouch model has been successfully used to confirm that a chemical of environmental concern can induce an inflammatory response in vivo.

Key Words: pollutants • organochloride • O₂^- production • IL-8 • murine air pouch

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