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Mechanisms of organophosphorus pesticide toxicity in the context of airway hyperreactivity and asthma
| Content Provider | eScholarship Repository: University of California |
|---|---|
| Author | Shaffo, Frances C Grodzki, Ana Cristina Fryer, Allison D Lein, Pamela J |
| Abstract | Numerous epidemiologic studies have identified an association between occupational exposures to organophosphorus pesticides (OPs) and asthma or asthmatic symptoms in adults. Emerging epidemiologic data suggest that environmentally relevant levels of OPs may also be linked to respiratory dysfunction in the general population and that in utero and/or early life exposures to environmental OPs may increase risk for childhood asthma. In support of a causal link between OPs and asthma, experimental evidence demonstrates that occupationally and environmentally relevant OP exposures induce bronchospasm and airway hyperreactivity in preclinical models. Mechanistic studies have identified blockade of autoinhibitory M2 muscarinic receptors on parasympathetic nerves that innervate airway smooth muscle as one mechanism by which OPs induce airway hyperreactivity, but significant questions remain regarding the mechanism(s) by which OPs cause neuronal M2 receptor dysfunction and, more generally, how OPs cause persistent asthma, especially after developmental exposures. The goals of this review are to 1) summarize current understanding of OPs in asthma; 2) discuss mechanisms of OP neurotoxicity and immunotoxicity that warrant consideration in the context of OP-induced airway hyperreactivity and asthma, specifically, inflammatory responses, oxidative stress, neural plasticity, and neurogenic inflammation; and 3) identify critical data gaps that need to be addressed in order to better protect adults and children against the harmful respiratory effects of low-level OP exposures. |
| File Format | |
| DOI | 10.1152/ajplung.00211.2018 |
| Alternate Webpage(s) | https://escholarship.org/uc/item/8cf2c2m0 |
| Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
| Issue Number | 4 |
| Volume Number | 315 |
| Language | English |
| Publisher Date | 2018-10-01 |
| Access Restriction | Open |
| Subject Keyword | Airway Hyperreactivity Eosinophils Macrophages Nerve-Immune Interactions Neurotoxicity Organophosphorus Pesticides Biomedical and Clinical Sciences Medical Physiology Cardiovascular Medicine and Haematology Prevention Climate-Related Exposures and Conditions Pediatric Asthma Lung 2.1 Biological and endogenous factors Respiratory Animals Bronchial Hyperreactivity Humans Organophosphorus Compounds Pesticides Physiology Respiratory System |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Physiology Physiology (medical) Pulmonary and Respiratory Medicine |
