title: In vivo hydroquinone exposure alters circulating neutrophil activities and impairs LPS-induced lung inflammation in mice.
abstract: Hydroquinone (HQ) is an environmental contaminant which causes immune toxicity. In this study, the effects of exposure to low doses of HQ on neutrophil mobilization into the LPS-inflamed lung were investigated. Male Swiss mice were exposed to aerosolized vehicle (control) or 12.5, 25 or 50ppm HQ (1h/day for 5 days). One hour later, oxidative burst, cell cycle, DNA fragmentation and adhesion molecules expressions in circulating neutrophils were determined by flow cytometry, and plasma malondialdehyde (MDA) levels were measured by HPLC. Also, 1h later the last exposures, inflammation was induced by LPS inhalation (0.1mg/ml/10min) and 3h later, the numbers of leukocytes in peripheral blood and in the bronchoalveolar lavage fluid (BALF) were determined using a Neubauer chamber and stained smears; adhesion molecules expressed on lung microvessel endothelial cells were quantified by immunohistochemistry; myeloperoxidase (MPO) activity was measured in the lung tissue by colorimetric assay; and cytokines in the BALF were determined by ELISA. In vivo HQ exposure augmented plasma MDA levels and oxidative activity of neutrophils, but did not cause alterations in cell cycle and DNA fragmentation. Under these conditions, the number of circulating leukocytes was not altered, but HQ exposure reduced LPS-induced neutrophil migration into the alveolar space, as these cells remained in the lung tissue. The impaired neutrophil migration into BALF may not be dependent on reduced cytokines secretions in the BALF and lung endothelial adhesion molecules expressions. However, HQ exposure increased the expression of β(2) and β(3) integrins and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in neutrophils, which were not further enhanced by fMLP in vitro stimulation, indicating that HQ exposure activates circulating neutrophils, impairing further stimulatory responses. Therefore, it has been shown, for the first time, that neutrophils are target of lower levels of in vivo HQ exposure, which may be considered in host defense in infectious diseases.
authors.affiliation: Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Brazil.
authors.forename: André Luiz Teroso
authors.initials: AL
authors.lastname: Ribeiro
authors.forename: Ana Lúcia Borges
authors.initials: AL
authors.lastname: Shimada
authors.forename: Cristina Bichels
authors.initials: CB
authors.lastname: Hebeda
authors.forename: Tiago Franco
authors.initials: TF
authors.lastname: de Oliveira
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: de Melo Loureiro
authors.forename: Walter Dos Reis Pereira
authors.initials: Wdos R
authors.lastname: Filho
authors.forename: Alcinéa Meigikos Dos Anjos
authors.initials: AM
authors.lastname: Santos
authors.forename: Wothan Tavares
authors.initials: WT
authors.lastname: de Lima
authors.forename: Sandra Helena Poliselli
authors.initials: SH
authors.lastname: Farsky
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D005434:Flow Cytometry; D006873:Hydroquinones / Q000008:administration & dosage / Q000633:toxicity*; D007249:Inflammation / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects
chemical_list: D015815:Cell Adhesion Molecules; D004785:Environmental Pollutants; D006873:Hydroquinones; D008070:Lipopolysaccharides; C031927:hydroquinone