Abstract
Neutrophil extracellular traps (NETs) are reticular structures formed by myeloperoxidase (MPO), histones, and neutrophil elastase (NE) that are released from neutrophils in response to pathogenic stimuli. Chlorpyrifos (CPF) is wildly used as an organophosphorus pesticide that causes a range of toxicological and environmental problems. Exposure to CPF can increase the production of neutrophils in carps, and this increase can be considered a biomarker of water pollution. To explore a relationship between NETs and CPF and its mechanism of influence, we treated neutrophils from the blood of carp with 1 μg/mL phorbol 12-myristate 13-acetate (PMA), 0.325 mg/L CPF, or 20 μM necrostatin-1 (Nec-1). The production of MPO and NETs was reduced in the CPF+PMA group compared with that in the PMA group. CPF can cause an increase in reactive oxygen species (ROS), while inhibiting respiratory burst caused by PMA stimulation. We found that the expression levels of protein-coupled receptor 84 (gpr84), dystroglycan (DAG), proto-oncogene serine/threonine kinase (RAF), protein kinase C (PKC), and mitogen-activated protein kinase 3 (MAPK3) in the CPF+PMA group were lower than those in the PMA group, indicating that the PKC-MAPK pathway was suppressed. The expression levels of cylindromatosis (CYLD), mixed lineage kinase domain-like pseudokinase (MLKL), receptor-interacting serine-threonine kinase 1 (RIP1), and receptor-interacting serine-threonine kinase 3 (RIP3) were increased, and the expression levels of caspase 8 were reduced by CPF, indicating that CPF may cause necroptosis. The addition of Nec-1 restored the number of NETs in the CPF+PMA group. The results indicate that CPF reduced the production of NETs by inhibiting respiratory burst and increasing necroptosis. The results contribute to the understanding of the immunotoxicological mechanism of CPF and provide a reference for comparative medical studies.
Highlights
Chlorpyrifos (CPF) has been one of the most widely used broad-spectrum organophosphorus pesticides in the world and a major environmental pollutant
Neutrophils can respond to various stimuli, such as phorbol 12-myristate 13-acetate (PMA), IL-8, or bacteria, by producing Neutrophil extracellular traps (NETs) [34]
After the examination of workers exposed to organophosphorus pesticides, Queiroz et al found that the killing of Candida albicans by neutrophils from the exposed workers was reduced [36]
Summary
Chlorpyrifos (CPF) has been one of the most widely used broad-spectrum organophosphorus pesticides in the world and a major environmental pollutant. Many countries have reported excessive residual levels of CPF in soil, water, fruits, vegetables, and aquatic animals [1]. It can inhibit the activity of cholinesterase and cause the accumulation of acetylcholine, leading to acute adverse effects, such as tremor, paralysis, convulsion, and coma [3, 4]. CPF can modulate the immune response by stimulating the antigen-presenting ability of the head kidney of the carp [8]. It had been reported that the innate immune system was disturbed by CPF in zebrafish [9]. Rats exposed to CPF had an altered number of T cells and B cells with variable degrees of changes relative to the control animals after 45 and 90 days at all tested exposure levels [10].
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