Macrophage tumoricidal mechanisms are selectively altered by prenatal chlordane exposure

Abstract

Macrophages (m phi) derived from mice treated in utero with chlordane show a significant delay of tumoricidal induction activity. In this study, m phi from chlordane-treated animals required a 48 h in vitro period of induction with interferon-gamma and lipopolysaccharide (IFN/LPS) before they could kill P815 targets. Similarly, m phi from chlordane-treated animals also failed to produce an immediate H2O2 burst upon perturbation. Conversely, their stimulated control m phi counterparts were tumoricidal by 2 h and exhibited a respiratory burst without any delay. Moreover, levels of the second messenger, inositol triphosphate (IP3), were significantly delayed in chlordane-treated animals following interaction with IFN/LPS. When nitrate/nitrite production was analyzed as an alternate mechanism for killing tumors, stimulated m phi from both normal and chlordane-treated animals responded equally. The data show that chlordane differentially introduces defects in m phi biochemical mechanisms associated with tumor killing.

Environmental toxicants and the developing immune system: A missing link in the global battle against infectious disease?

“…For example, developmental exposure of rodents to atrazine, one of the most commonly used herbicides, altered proliferative responses in both B and T lymphocytes [103, 104]. Alterations in immune function after gestational exposure to chlordane have been well studied, and include decreased killing of tumor cells by macrophages, altered NK cell activity, altered T lymphocyte responses, and enhanced survival to influenza virus infection [105–109]. Further assessment of disease-related immune endpoints is needed in both animal models of developmental exposure and in the human population.…”

Hydrogen peroxide-induced Akt phosphorylation regulates Bax activation

“…In contrast, ROS are directly and indirectly involved in physiological signaling pathways [9, 10]. Low levels of ROS regulates cellular function in tumor cells [11], T cells [9], and macrophages [12]. …”

Sub-acute exposure to the herbicide atrazine suppresses cell immune functions in adolescent mice

“…However, the immune system is still developing in the early postnatal period. The developing immune system is more sensitive to xenobiotic exposure than the adult immune system (26)(27)(28). A continuous remodeling of the primary and secondary immune organs occurs in mice throughout their lives, i.e., a decline in the relative weight of the thymus, spleen, and lymph nodes occurs before puberty, while only the thymus continues to involute after puberty (29).…”