Immunotoxicity of organophosphorus compounds

Esa, Ahmed H.; Warr, Glenn A.; Newcombe, David S.

doi:10.1016/0090-1229(88)90093-1

Cited by 39 publications

(5 citation statements)

References 22 publications

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“… 46–48 Other pesticides have been shown to directly impact antigen presentation, and although this has not been reported for pyrethroids it is possible that their effects on immune cells may explain the synergism with the MHC-II locus to increase risk for PD. 49 The identified combined risk conferred by the rs3129882 G allele and pyrethroids may be explained by complex interactions that impact both the nervous system and the immune system to initiate PD pathogenesis through voltage-gated sodium channels that are known targets of this class of pesticides. The follow-up of the PEG patients-only cohort suggested no association between the G allele and disease severity/progression ( Supplementary Table S3 ).…”

Section: Discussionmentioning

confidence: 99%

Common genetic variant association with altered HLA expression, synergy with pyrethroid exposure, and risk for Parkinson’s disease: an observational and case–control study

Kannarkat

Cook

Lee

et al. 2015

npj Parkinson's Disease

123

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Background/Objectives The common non-coding single nucleotide polymorphism (SNP) rs3129882 in HLA-DRA is associated with risk for idiopathic Parkinson’s disease (PD). The location of the SNP in the major histocompatibility complex class II (MHC-II) locus implicates regulation of antigen presentation as a potential mechanism by which immune responses link genetic susceptibility to environmental factors in conferring lifetime risk for PD. Methods For immunophenotyping, blood cells from 81 subjects were analyzed by qRT-PCR and flow cytometry. A case-control study was performed on a separate cohort of 962 subjects to determine association of pesticide exposure and the SNP with risk of PD. Results Homozygosity for G at this SNP was associated with heightened baseline expression and inducibility of MHC class II molecules in B cells and monocytes from peripheral blood of healthy controls and PD patients. In addition, exposure to a commonly used class of insecticide, pyrethroids, synergized with the risk conferred by this SNP (OR = 2.48, p = 0.007), thereby identifying a novel gene-environment interaction that promotes risk for PD via alterations in immune responses. Conclusions In sum, these novel findings suggest that the MHC-II locus may increase susceptibility to PD through presentation of pathogenic, immunodominant antigens and/or a shift toward a more pro-inflammatory CD4+ T cell response in response to specific environmental exposures, such as pyrethroid exposure through genetic or epigenetic mechanisms that modulate MHC-II gene expression.

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Section: Discussionmentioning

confidence: 99%

Common genetic variant association with altered HLA expression, synergy with pyrethroid exposure, and risk for Parkinson’s disease: an observational and case–control study

Kannarkat

Cook

Lee

et al. 2015

npj Parkinson's Disease

123

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“…Environmental exposures have been found to influence inflammation, for example by impacting antigen presentation. [100]…”

Section: Introductionmentioning

confidence: 99%

Of Pesticides and Men: a California Story of Genes and Environment in Parkinson’s Disease

Ritz

Paul

Bronstein³

2016

Curr Envir Health Rpt

119

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At the start of the post-genomics era, most Parkinson’s disease (PD) etiology cannot be explained by our knowledge of genetic or environmental factors alone. For more than a decade, we have explored gene-environment (GxE) interactions possibly responsible for the heterogeneity of genetic as well as environmental results across populations. We developed three pesticide exposure measures (ambient due to agricultural applications, home and garden use, occupational use) in a large population-based case-control study of incident PD in central California. Specifically, we assessed interactions with genes responsible for pesticide metabolism (PON1); transport across the blood brain barrier (ABCB1); pesticides interfering with or depending on dopamine transporter activity (DAT) and dopamine metabolism (ALDH2); impacting mitochondrial function via oxidative/nitrosative stress (NOS1) or proteasome inhibition (SKP1); and contributing to immune dysregulation (HLA-DR). These studies established some specificity for pesticides’ neurodegenerative actions, contributed biologic plausibility to epidemiologic findings, and identified genetically susceptible populations.

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“…Scientific evidence of in vivo and in vitro assays demonstrated the toxic effect of OPs on the immune response of several organisms ( Figure 1 ), but the non-neuronal molecular mechanisms of these effects are not fully elucidated. In this sense, it is suggested that the reported effects could be related to interactions of active metabolites of OPs on nicotinic, G-protein-coupled muscarinic (GPCR) and interleukin (ILR) receptors, altering the signaling pathways and gene expression in cells of innate and adaptive immunity, thereby modulating processes of phagocytosis, respiratory burst, lymphoproliferation, cellular senescence, neutrophil extracellular traps (NETs), cell death, complement, antibody production, cytokines, chemokines, and antigen presentation [ 18 , 19 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Organophosphate-Pesticide-Mediated Immune Response Modulation in Invertebrates and Vertebrates

Bernal-González

Covantes-Rosales

Camacho-Pérez

et al. 2023

IJMS

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Organophosphate pesticides (OPs) have greatly facilitated food production worldwide, and their use is not limited to agriculture and the control of pests and disease vectors. However, these substances can directly affect the immune response of non-target organisms. In this sense, exposure to OPs can have negative effects on innate and adaptive immunity, promoting deregulation in humoral and cellular processes such as phagocytosis, cytokine expression, antibody production, cell proliferation, and differentiation, which are crucial mechanisms for host defense against external agents. This review focuses on the scientific evidence of exposure to OPs and their toxic effects on the immune system of non-target organisms (invertebrates and vertebrates) from a descriptive perspective of the immuno-toxic mechanisms associated with susceptibility to the development of bacterial, viral, and fungal infectious diseases. During the exhaustive review, we found that there is an important gap in the study of non-target organisms, examples of which are echinoderms and chondrichthyans. It is therefore important to increase the number of studies on other species directly or indirectly affected by Ops, to assess the degree of impact at the individual level and how this affects higher levels, such as populations and ecosystems.

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Immunotoxicity of organophosphorus compounds

Cited by 39 publications

References 22 publications

Common genetic variant association with altered HLA expression, synergy with pyrethroid exposure, and risk for Parkinson’s disease: an observational and case–control study

Common genetic variant association with altered HLA expression, synergy with pyrethroid exposure, and risk for Parkinson’s disease: an observational and case–control study

Of Pesticides and Men: a California Story of Genes and Environment in Parkinson’s Disease

Organophosphate-Pesticide-Mediated Immune Response Modulation in Invertebrates and Vertebrates

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