title: Airborne pollutant ROFA enhances the allergic airway inflammation through direct modulation of dendritic cells in an uptake-dependent mechanism.
abstract: Studies suggest that airborne pollutants are important cofactors in the exacerbation of lung diseases. The role of DC on the exacerbation of lung inflammation induced by particulate matter pollutants is unclear. We evaluated the effects of residual oil fly ash (ROFA) on the phenotype and function of bone marrow-derived dendritic cells (BMDCs) in vitro and lung dendritic cells (DCs) in vivo, and the subsequent T-cell response. In a model of asthma, exposure to ROFA exacerbated pulmonary inflammation, which was attributed to the increase of eosinophils, IL-5- and IFN-γ-producing T cells, and goblet cells as well as decreased number of Treg and pDC. However, the ROFA showed no ability to modulate the production of anaphylactic IgE. In vitro studies showed that ROFA directly induced the maturation of DCs up-regulating the expression of co-stimulatory molecules and cytokines and MMP production in an uptake-dependent and oxidative stress-dependent manner. Furthermore, ROFA-pulsed BMDC transferred to allergic mice exacerbated eosinophilic inflammation as well as promoted increased epithelial and goblet cells changes. Thus, pollutants may constitute an important and risk factor in the exacerbation of asthma with inhibition of the negative regulatory signals in the lung, with enhanced mDC activation that sustains the recruitment of effector T lymphocytes and eosinophil.
authors: Immunoregulation Unit, Special Laboratory of Applied Toxinology, Butantan Institute, Av. Vital Brazil, 1500, Sao Paulo CEP 05503-009, SP, Brazil; Laboratório de Terapêutica Experimental (LIM20), Faculdade de Medicina da USP, Av. Dr Arnaldo, 455, Sala 1220, Sao Paulo CEP 01246-903, SP, Brazil.
authors: Fernanda Magalhaes
authors: FM
authors: Arantes-Costa
authors: Immunoregulation Unit, Special Laboratory of Applied Toxinology, Butantan Institute, Av. Vital Brazil, 1500, Sao Paulo CEP 05503-009, SP, Brazil.
authors: Lidiane Zito
authors: LZ
authors: Grund
authors: Laboratório de Terapêutica Experimental (LIM20), Faculdade de Medicina da USP, Av. Dr Arnaldo, 455, Sala 1220, Sao Paulo CEP 01246-903, SP, Brazil.
authors: Milton Arruda
authors: MA
authors: Martins
authors: Immunoregulation Unit, Special Laboratory of Applied Toxinology, Butantan Institute, Av. Vital Brazil, 1500, Sao Paulo CEP 05503-009, SP, Brazil. Electronic address: carla.lima@butantan.gov.br.
authors: Carla
authors: C
authors: Lima
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D060729:Coal Ash / Q000008:administration & dosage*; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004705:Endocytosis; D004804:Eosinophils / Q000276:immunology; D005260:Female; D020397:Goblet Cells / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation; D008807:Mice, Inbred BALB C; D052638:Particulate Matter / Q000008:administration & dosage*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D060729:Coal Ash; D015848:Interleukin-5; D052638:Particulate Matter; D007371:Interferon-gamma
keywords: Asthma; Dendritic cell; Particulate matter; ROFA; Regulatory cell