| Title: | Combined adjuvant effects of ambient vapor-phase organic components and particulate matter potently promote allergic sensitization and Th2-skewing cytokine and chemokine milieux in mice: The importance of mechanistic multi-pollutant research |
| Author(s): | Li N; Lewandowski RP; Sidhu D; Holz C; Jackson-Humbles D; Eiguren-Fernandez A; Akbari P; Cho AK; Harkema JR; Froines JR; Wagner JG; |
| Address: | "Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA. Electronic address: ninali.8880@gmail.com. Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA. Department of Environmental Health Sciences, School of Public Health, University of California Los Angeles, Los Angeles, CA, USA. Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA. Electronic address: wagnerja@msu.edu" |
| DOI: | 10.1016/j.toxlet.2021.11.019 |
| ISSN/ISBN: | 1879-3169 (Electronic) 0378-4274 (Linking) |
| Abstract: | "Although exposure to ambient particulate matter (PM) is linked to asthma, the health effects of co-existing vapor-phase organic pollutants (vapor) and their combined effects with PM on this disease are poorly understood. We used a murine asthma model to test the hypothesis that exposure to vapor would enhance allergic sensitization and this effect would be further strengthened by co-existing PM. We found that vapor and PM each individually exerted adjuvant effects on OVA sensitization. Co-exposure to vapor and PM during sensitization further enhanced allergic lung inflammation and OVA-specific antibody production which was accompanied by pulmonary cytokine/chemokine milieu that favored T-helper 2 immunity (i.e. increased IL-4, downregulation of Il12a and Ifng, and upregulation of Ccl11 and Ccl8). TNFalpha, IL-6, Ccl12, Cxcl1 and detoxification/antioxidant enzyme responses in the lung were pollutant-dependent. Inhibition of lipopolysaccharide-induced IL-12 secretion from primary antigen-presenting dendritic cells correlated positively with vapor's oxidant potential. In conclusion, concurrent exposure to vapor and PM led to significantly exaggerated adjuvant effects on allergic lung inflammation which were more potent than that of each pollutant type alone. These findings suggest that the effects of multi-component air pollution on asthma may be significantly underestimated if research only focuses on a single air pollutant (e.g., PM)" |
| Keywords: | "Animals Asthma/*chemically induced Cytokines/genetics/*metabolism Down-Regulation Drug Interactions Female Gene Expression Regulation/drug effects Hypersensitivity/*etiology Mice Mice, Inbred BALB C Ovalbumin/toxicity Particle Size Particulate Matter/*tox;" |
| Notes: | "MedlineLi, Ning Lewandowski, Ryan P Sidhu, Damansher Holz, Carine Jackson-Humbles, Daven Eiguren-Fernandez, Arantzazu Akbari, Peyman Cho, Arthur K Harkema, Jack R Froines, John R Wagner, James G eng Netherlands 2021/12/06 Toxicol Lett. 2022 Mar 1; 356:21-32. doi: 10.1016/j.toxlet.2021.11.019. Epub 2021 Dec 1" |
