title: In vivo hydroquinone exposure impairs MCP-1 secretion and monocyte recruitment into the inflamed lung.
abstract: Alveolar macrophages (AMs) are important cells in the resolution of the inflammatory process and they come into direct contact with inhaled pollutants. Hydroquinone (HQ) is an environmental pollutant and a component of cigarette smoke that causes immunosuppressive effects. In the present work, we showed that mice exposed to low levels of aerosolized HQ (25 ppm; 1 h/day/5 days) presented impaired mononuclear cell migration to the lipopolysaccharide (LPS)-inflamed lung. This may have been due to reduced monocyte chemoattractant protein-1 (MCP-1) secretion into bronchoalveolar lavage fluid (BALF), and it was not related to alterations to mononuclear cell mobilization into the blood or adhesion molecules expression on mononuclear cell membranes. Corroborating the actions of HQ on MCP-1 secretion, reduced MCP-1 concentrations were also found in the supernatant of ex vivo AM and tracheal tissue collected from HQ-exposed mice. A direct action of HQ on MCP-1 secretion, resulting from impaired gene synthesis, was verified by in vitro incubation of naive AMs or tracheal tissue with HQ. The role of reduced levels of MCP-1 in the BALF on monocyte migration was analysed in the human monocytic lineage THP-1 in in vitro chemotaxis assays, which showed that the reduced concentrations of MCP-1 found in the BALF or cell supernatants from HQ-exposed mice impaired cell migration. Considering the fact that MCP-1 presents a broad spectrum of actions on pathophysiological conditions and that resident mononuclear cells are involved in lung tissue homeostasis and in immune host defence, the mechanism of HQ toxicity presented herein might be relevant to the genesis of infectious lung diseases in smokers and in inhabitants of polluted areas.
authors.affiliation: Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Brazil.
authors.forename: Ana Lúcia Borges
authors.initials: AL
authors.lastname: Shimada
authors.forename: André Luiz Teroso
authors.initials: AL
authors.lastname: Ribeiro
authors.forename: Simone Marques
authors.initials: SM
authors.lastname: Bolonheis
authors.forename: Viviane
authors.initials: V
authors.lastname: Ferraz-de-Paula
authors.forename: Cristina Bichels
authors.initials: CB
authors.lastname: Hebeda
authors.forename: Sandra Helena Poliselli
authors.initials: SH
authors.lastname: Farsky
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism*; D004785:Environmental Pollutants / Q000633:toxicity; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D016676:Macrophages, Alveolar / Q000166:cytology; D008297:Male; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D012906:Smoke; D014026:Nicotiana
chemical_list: D018932:Chemokine CCL2; D004785:Environmental Pollutants; D006873:Hydroquinones; D007166:Immunosuppressive Agents; D012906:Smoke; C031927:hydroquinone