title: Absorption of PCB126 by upper airways impairs G protein-coupled receptor-mediated immune response.
abstract: PCB126 is a dioxin-like polychlorinated biphenyl (PCB) environmental pollutant with a significant impact on human health, as it bioaccumulates and causes severe toxicity. PCB126-induced immune toxicity has been described, although the mechanisms have not been fully elucidated. In this study, an in vivo protocol of PCB126 intoxication into male Wistar rats by intranasal route was used, which has not yet been described. The intoxication was characterised by PCB126 accumulation in the lungs and liver, and enhanced aryl hydrocarbon receptor expression in the liver, lungs, kidneys, and adipose tissues. Moreover, an innate immune deficiency was characterised by impairment of adhesion receptors on blood leukocytes and by reduced blood neutrophil locomotion and oxidative burst activation elicited by ex vivo G protein-coupled receptor (GPCR) activation. Specificity of PCB126 actions on the GPCR pathway was shown by normal burst oxidative activation evoked by Toll-like receptor 4 and protein kinase C direct activation. Moreover, in vivo PCB180 intoxication did not alter adhesion receptors on blood leukocytes either blood neutrophil locomotion, and only partially reduced the GPCR-induced burst oxidative activation on neutrophils. Therefore, a novel mechanism of in vivo PCB126 toxicity is described which impairs a pivotal inflammatory pathway to the host defence against infections.
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-900 Brazil.
authors.forename: Ana Lúcia B
authors.initials: AL
authors.lastname: Shimada
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-900 Brazil.
authors.forename: Wesley S
authors.initials: WS
authors.lastname: Cruz
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-900 Brazil.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Loiola
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-900 Brazil.
authors.forename: Carine C
authors.initials: CC
authors.lastname: Drewes
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-900 Brazil.
authors.forename: Fabiane
authors.initials: F
authors.lastname: Dörr
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-900 Brazil.
authors.forename: Natália G
authors.initials: NG
authors.lastname: Figueiredo
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-900 Brazil.
authors.forename: Ernani
authors.initials: E
authors.lastname: Pinto
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-900 Brazil.
authors.forename: Sandra H P
authors.initials: SH
authors.lastname: Farsky
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000281:Administration, Intranasal; D000818:Animals; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D007113:Immunity, Innate / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D065588:Nasal Absorption; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D017208:Rats, Wistar; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D018336:Receptors, Aryl Hydrocarbon; D043562:Receptors, G-Protein-Coupled; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl