Alterations in macrophage phagocytosis and inflammatory tone following exposure to the organochlorine compounds oxychlordane and trans-nonachlor

The role of macrophages in the innate immune response cannot be underscored however recent studies have demonstrated that both resident and recruited macrophages have critical roles in the pathogenesis of metabolic dysfunction. Given the recent data implicating exposure to persistent organic pollutants (POPs) in the pathogenesis of metabolic diseases, the current study was designed to examine the effects of the highly implicated organochlorine (OC) compounds oxychlordane and trans-nonachlor on overall macrophage function. Murine J774A.1 macrophages were exposed to trans-nonachlor or oxychlordane (0 - 20 mu M) for 24 hours then phagocytosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential, caspase activities, pro-inflammatory cytokine production, and macrophage plasticity were assessed. Overall, exposure to oxychlordane significantly decreased macrophage phagocytosis while both OC compounds significantly increased ROS generation. Exposure to trans-nonachlor significantly increased secretion of tumor necrosis factor alpha (TNF alpha) and interleukin-6 whereas oxychlordane had a biphasic effect on TNF alpha secretion. However, both oxychlordane and trans-nonachlor decreased basal expression of the M1 pro-inflammatory marker cyclooxygenase 2. Taken together, these data indicate that exposure to these two OC compounds have both compound and concentration dependent effects on macrophage function which may alter both the innate immune response and impact metabolic function of key organs involved in metabolic diseases.