Activation of human neutrophils by chiordane: induction of superoxide production and phagocytosis but not chemotaxis or apoptosis

Abstract

We have recently reported that human neutrophils are important targets of different xenobiotics, including chemicals of environmental concern. In the present study, we found that chlordane was not toxic for human neutrophils incubated for up to 24 h with concentrations ranging from 0.1 to 50 pg/nl. Chlordane was found to induce neutrophil superoxide production (Oz–) in a concentration–dependent fashion and its potency to induce this response was found to be similar to phorbol 12-myristate 13-acetate (PMA), a classical neutrophil agonist. The use of different transduction signal inhibitors (genistein, pertussis toxin, staurosporine, and calphostin C) indicates that, as for PMA, chlordane induces 02 production via protein kinase C (PKC). In this respect, staurosporine and calphostin C were found to inhibit chlordane–and PMAinduced 02 production by 65% and 72%, and by 83% and 85%o, respectively. Chlordane was also found to significantly enhance neutrophil phagocytosis of opsonized sheep red blood cells (SRBCs). Despite these effects, chlordane did not alter neutrophil apoptosis as assessed by cytology (Diff-Quick staining) and by flow cytometry (CD-16 expression). In addition, chlordane did notalterneutrophil chemotaxis (48–well Boyden chamber). Cells were, however, responsive as they were activated by the well–characterized interleukin (IL)–8 chemokine. We conclude that chlordane can activate 02 production by a PKC-dependent mechanism and induce phagocytosis without altering chemotaxis and apoptosis. Chlordane must be added to a growing list of environmental contaminants that share some pro–inflammatory properties.