Suppression of chemokine-induced chemotaxis of monkey neutrophils and monocytes by chlorinated hydrocarbon insecticides.
Chemokines, characterized as pro-inflammatory chemicals made by the immune system, consist of a family of low molecular weight proteins with potent in vitro chemotactic activity causing leukocyte accumulation in vivo. This study determines the effects of organochlorine pesticide exposure on the chemotactic functions of monkey neutrophils and monocytes, using a 48-well chemotaxis chamber. Chemokines IL-8 (interleukin-8) and RANTES were used as the chemoattractants to induce chemotaxis among these monkey leukocytes. Monkey neutrophils or monocytes were first treated with heptachlor, chlordane or toxaphene for 1 hour at 37 degrees C, and the number of cells migrating toward 200 ng/ml IL-8 (for neutrophils) or 100 ng/ml RANTES (for monocytes) were scored. Inhibition of chemotaxis was seen with all samples after treatment with heptachlor, chlordane and toxaphene at concentrations from as low as 10(-14) M to 10(-5) M. Among the three compounds studied, toxaphene was the least effective in preventing monocytes from migrating toward RANTES. The ability of these pesticides to inhibit chemotaxis did not correlate directly with their potential apoptotic effects on the monkey leukocytes. These studies suggest that exposure to organochlorine pesticides may alter leukocyte-related immune functions.
Miyagi
T
T
Department of Medical Pharmacology and Toxicology, School of Medicine, University of California, Davis 95616, USA.
Lam
K M
KM
Chuang
L F
LF
Chuang
R Y
RY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D018946:Chemokine CCL5 / Q000494:pharmacology; D018925:Chemokines / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D002706:Chlordan / Q000494:pharmacology; D004247:DNA / Q000032:analysis; D006533:Heptachlor / Q000494:pharmacology; D007306:Insecticides / Q000494:pharmacology*; D016209:Interleukin-8 / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D014112:Toxaphene / Q000494:pharmacology
D018946:Chemokine CCL5; D018925:Chemokines; D007306:Insecticides; D016209:Interleukin-8; D002706:Chlordan; D006533:Heptachlor; D014112:Toxaphene; D004247:DNA