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Characterization of Human Monocyte-derived Dendritic Cells by Imaging Flow Cytometry: A Comparison between Two Monocyte Isolation Protocols
Published on: October 18, 2016
Influence of organophosphate poisoning on human dendritic cells
Marina Schäfer1, Franziska Koppe, Bernhard Stenger
1Institute of Pathology, Repair-Lab, Johannes Gutenberg University Mainz, Germany.
Abstract:
Organophosphourus compounds (OPC, including nerve agents and pesticides) exhibit acute toxicity by inhibition of acetylcholinesterase. Lung affections are frequent complications and a risk factor for death. In addition, epidemiological studies reported immunological alterations after OPC exposure. In our experiments we investigated the effects of organophosphourus pesticides dimethoate and chlorpyrifos on dendritic cells (DC) that are essential for the initial immune response, especially in the pulmonary system. DC, differentiated from the monocyte cell line THP-1 by using various cytokines (IL-4, GM-CSF, TNF-α, Ionomycin), were exposed to organophosphourus compounds at different concentrations for a 24h time period. DC were characterized by flow cytometry and immunofluorescence using typical dendritic cell markers (e.g., CD11c, CD209 and CD83). After OPC exposure we investigated cell death, the secretion profile of inflammatory mediators, changes of DC morphology, and the effect on protein kinase signalling pathways. Our results revealed a successful differentiation of THP-1 into DC. OPC exposure caused a significant concentration-dependent influence on DC: Dendrites of the DC were shortened and damaged, DC-specific cell surface markers (i.e., CD83and CD209) decreased dramatically after chlorpyrifos exposure. Interestingly, the effects caused by dimethoate were in general less pronounced. The organophosphourus compounds affected the release of inflammatory cytokines, such as IL-1ß and IL-8. The anti-inflammatory cytokine IL-10 was significantly down regulated. Protein kinases like the Akt family or ERK, which are essential for cell survival and proliferation, were inhibited by both OPC. These findings indicate that the tested organophosphourus compounds induced significant changes in cell morphology, inhibited anti-inflammatory cytokines and influenced important protein signalling pathways which are involved in regulation of apoptosis. Thus our results highlight novel aspects -apparently independent of AChE inhibition- of OPC poisoning with regard to lung toxicity. Our findings contribute to the basic understanding of pulmonary complications caused by OPC poisoning.
Insights
Organophosphorus compounds (OPC) damage dendritic cells, impacting immune responses in the lungs. These pesticides alter cell structure and signaling pathways, independent of acetylcholinesterase inhibition, contributing to lung toxicity.
Area of Science:
- Toxicology
- Immunology
- Cell Biology
Background:
- Organophosphorus compounds (OPC) are acutely toxic via acetylcholinesterase inhibition, frequently causing lung complications and death.
- Epidemiological studies suggest OPC exposure can lead to immunological alterations.
Purpose of the Study:
- To investigate the effects of dimethoate and chlorpyrifos on dendritic cells (DCs), crucial for pulmonary immune responses.
- To explore OPC-induced changes in DC morphology, cell death, inflammatory mediator secretion, and protein kinase signaling.
Main Methods:
- Differentiated THP-1 monocytes into DCs using cytokines (IL-4, GM-CSF, TNF-α, Ionomycin).
- Exposed differentiated DCs to varying concentrations of dimethoate and chlorpyrifos for 24 hours.
- Characterized DCs using flow cytometry and immunofluorescence; analyzed cell death, cytokine profiles, morphology, and protein kinase activity (Akt, ERK).
Main Results:
- OPC exposure caused concentration-dependent damage to DC dendrites and reduced expression of DC markers (CD83, CD209), particularly with chlorpyrifos.
- OPCs altered the secretion of inflammatory cytokines (IL-1β, IL-8) and significantly downregulated the anti-inflammatory cytokine IL-10.
- Inhibition of essential protein kinases (Akt, ERK) involved in cell survival and proliferation was observed.
Conclusions:
- Dimethoate and chlorpyrifos induce significant changes in DC morphology and function, impacting immune signaling pathways.
- OPC-induced pulmonary toxicity may involve mechanisms beyond acetylcholinesterase inhibition, affecting dendritic cell function and inflammatory responses.
- These findings offer novel insights into the pathogenesis of lung complications following organophosphorus pesticide exposure.
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