MARIANGELA MACCHIONE
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
13 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 13
- Effects of Intrauterine Exposure to Concentrated Ambient Particles on Mice Offspring Sensitized with House Dust Mite(2017) BRITO, Jose; ARANTES-COSTA, Fernanda Magalhaes; GUIMARAES, Eliane Tigre; VIEIRA, Rodolfo de Paula; MACCHIONE, Mariangela; MAUAD, Thais
- Effects of air pollution on inflammation of respiratory system: Differences between male and female(2015) YOSHIZAKI, Kelly; LINO-DOS-SANTOS-FRANCO, Adriana; BRITO, Jose Mara; SANTOS, Thais Moraes Nascimento; VASCONCELOS, Perola; MAUAD, Thais; SALDIVA, Paulo Hilario Nascimento; MACCHIONE, Mariangela
- Enriched inorganic compounds in diesel exhaust particles induce mitogen-activated protein kinase activation, cytoskeleton instability, and cytotoxicity in human bronchial epithelial cells(2015) SERIANI, Robson; JUNQUEIRA, Mara S.; CARVALHO-SOUSA, Claudia E.; ARRUDA, Alessandra Ct.; MARTINEZ, Diana; ALENCAR, Adriano M.; GARIPPO, Ana L.; BRITO, Jose Mara; MARTINS, Milton A.; SALDIVA, Paulo H. N.; NEGRI, Elnara M.; MAUAD, Thais; MACCHIONE, MariangelaThis study assessed the effects of the diesel exhaust particles on ERR and JNK MAPKs activation, cell rheology (viscoelasticity), and cytotoxicity in bronchial epithelial airway cells (BEAS-2B). Crude DEP and DEP after extraction with hexane (DEP/HEX) were utilized. The partial reduction of some DEP/HEX organics increased the biodisponibility of many metallic elements. JNK and ERR were activated simultaneously by crude DEP with no alterations in viscoelasticity of the cells. Mitochondrial activity, however, revealed a decrease through the MIT assay. DEP/HEX treatment increased viscoelasticity and cytotoxicity (membrane damage), and also activated JNK. Our data suggest that the greater bioavailability of metals could be involved in JNK activation and, consequently, in the reduction of fiber coherence and increase in the viscoelasticity and cytotoxicity of BEAS cells. The adverse findings detected after exposure to crude DEP and to DEP/HEX reflect the toxic potential of diesel compounds. Considering the fact that the cells of the respiratory epithelium are the first line of defense between the body and the environment, our data contribute to a better understanding of the pathways leading to respiratory cell injury and provide evidence for the onset of or worsening of respiratory diseases caused by inorganic compounds present in DEP.
conferenceObject Effects Of Air Pollution On Estrogen And Dioxin/aryl Hydrocarbon Receptors Gene Expression In Nasal Epithelium Of Female/male Mice(2013) YOSHIZAKI, K.; BRITO, J.; FUZIWARA, C.; SANTOS, T.; KIMURA, E.; MAUAD, T.; SALDIVA, P.; MACCHIONE, M.- Acute exposure to diesel and sewage biodiesel exhaust causes pulmonary and systemic inflammation in mice(2018) BRITO, Jose Mara de; MAUAD, Thais; CAVALHEIRO, Guilherme Franco; YOSHIZAKI, Kelly; ANDRE, Paulo Afonso de; LICHTENFELS, Ana Julia F. C.; GUIMARAES, Eliane Tigre; RIVERO, Dolores Helena Rodriguez Ferreira; ANTONANGELO, Leila; OLIVEIRA, Luciano Basto; PEDROSO, Luiz Roberto Martins; MACCHIONE, Mariangela; SALDIVA, Paulo Hilario NascimentoBiodiesel is a renewable energy source that reduces particle emission, but few studies have assessed its effects. To assess the effects of acute inhalation of two doses (600 and 1200 mu g/m(3)) of diesel (DE) and biodiesel (BD) fuels on the inflammatory pulmonary and systemic profile of mice. Animals were exposed for 2 h in an inhalation chamber inside the Container Laboratory for Fuels. Heart rate, heart rate variability (HRV) and blood pressure were determined 30 min after exposure. After 24 h. we analyzed the lung inflammation using bronchoalveolar lavage fluid (BALF); neutrophil and macrophage quantification in the lung parenchyma was performed, and blood and bone marrow biomarkers as well as receptor of endothelin-A (ET-Ar), receptor of endothelin-B (ET-Br), vascular cell adhesion molecule 1 (VCAM-1), inducible nitric oxide synthase (iNOs) and isoprostane (ISO) levels in the pulmonary vessels and bronchial epithelium were evaluated. HRV increased for BD600, D600 and D1200 compared to filtered air (FA). Both fuels (DE and BD) produced alterations in red blood cells independent of the dose. BALI from the BD600 and BD1200 groups showed an increase in neutrophils compared to those of the FA group. Numeric density of the polyrnorphonuclear and mononudear cells was elevated with BD600 compared to FA. In the peribronchiolar vessels, there was an increase in ET-Ar and ET-Br expression following BD600 compared to IA; and there was a reduction in the iNOs expression for BD1200 and the VCAM-1 for D1200 compared to FA. In the bronchial epithelium, there was an increase in ETAr at BD600, ET-Br at two doses (600 and 1200 mu g/m(3)) of DE and BD, iNOs at D600 and VCAM-1 at BD1200 and D600; all groups were compared to the FA group. Acute exposure to DE and BD derived from sewage methyl esters triggered pulmonary and cardiovascular inflammatory alterations in mice.
conferenceObject The effects of concentrated air pollution by gender: Experimental study in mice(2014) YOSHIZAKI, Kelly; FUZIWARA, Cesar S.; BRITO, Jose Mara; SANTOS, Thais M. N.; KIMURA, Edna T.; CORREIA, Aristides T.; VASCONCELOS, Perola; SILVA, Luiz F. F.; MAUAD, Thais; SALDIVA, Paulo H. N.; MACCHIONE, Mariangela- The effects of urban particulate matter on the nasal epithelium by gender: An experimental study in mice(2016) YOSHIZAKI, K.; FUZIWARA, C. S.; BRITO, J. M.; SANTOS, T. M. N.; KIMURA, E. T.; CORREIA, A. T.; AMATO-LOURENCO, L. F.; VASCONCELLOS, P.; SILVA, L. F.; BRENTANI, M. M.; MAUAD, T.; SALDIVA, P. H. N.; MACCHIONE, M.Nose is the first portion of the respiratory system into contact with air pollution particles, including organic compounds that could act as endocrine releasers. The objective was to identify and quantify estrogenic receptor-beta (ER beta), aryl hydrocarbon receptor (AhR), the cytochrome P450 enzymes CYP1A1, 1A2, 1B1, and mucus profile in the nasal epithelium of mice. BALB/c mice male (n = 32) and female (n = 82) in proestrus, estrus and diestrus were divided into two groups: 1) exposed to ambient air; 2) concentrated ambient particles (CAPs) to achieve an accumulated dose (concentration vs. time product) of 600 mu g/m(3), the time of the exposure was controlled to ensure the same concentration for all groups (5 days per week for 40-51 days). RT-PCR (Er beta-1, Er beta-2, Ahr, Cyp1a1, Cyp1a2, Cyp1b1), immunohistochemistry and morphometry (ER(3, AhR) were used to analyze. The mucus profiles were examined using acid (Aldan Blue) and neutral (periodic acid Schiff's) stains. Exposed females had significantly lower levels of Er beta-2 mRNA than exposed males (p = 0.036). Cyp1b1 mRNA in diestrus females was significantly lower in the CAP-exposed group compared with the ambient air group (p <= 0.05). ER beta expression in the epithelium and submucosa nucleus was lower in estrus exposed to CAPs compared with ambient air. CAPs increases AhR in the epithelium (p = 0.044) and submucosa (p = 0.001) nucleus of female when compared with male mice. Exposure to CAPs, also led to relatively increased acidic content in the mucus of males (p = 0.048), but decreased acidic content in that of females (p = 0.04). This study revealed sex dependent responses to air pollution in the nasal epithelium that may partially explain the predisposition of females to airway respiratory diseases.
- Chronic exposure of diesel exhaust particles induces alveolar enlargement in mice(2015) YOSHIZAKI, Kelly; BRITO, Jose Mara; MORIYA, Henrique T.; TOLEDO, Alessandra C.; FERZILAN, Sandra; OLIVEIRA, Ana Paula Ligeiro de; MACHADO, Isabel D.; FARSKY, Sandra H. P.; SILVA, Luiz F. F.; MARTINS, Milton A.; SALDIVA, Paulo H. N.; MAUAD, Thais; MACCHIONE, MariangelaBackground: Diesel exhaust particles (DEPs) are deposited into the respiratory tract and are thought to be a risk factor for the development of diseases of the respiratory system. In healthy individuals, the timing and mechanisms of respiratory tract injuries caused by chronic exposure to air pollution remain to be clarified. Methods: We evaluated the effects of chronic exposure to DEP at doses below those found in a typical bus corridor in Sao Paulo (150 mu g/m(3)). Male BALB/c mice were divided into mice receiving a nasal instillation: saline (saline; n = 30) and 30 mu g/10 mu L of DEP (DEP; n = 30). Nasal instillations were performed five days a week, over a period of 90 days. Bronchoalveolar lavage (BAL) was performed, and the concentrations of interleukin (IL)-4, IL-10, IL-13 and interferon-gamma (INF-gamma) were determined by ELISA-immunoassay. Assessment of respiratory mechanics was performed. The gene expression of Muc5ac in lung was evaluated by RT-PCR. The presence of IL-13, MAC2+ macrophages, CD3+, CD4+, CD8+ T cells and CD20+ B cells in tissues was analysed by immunohistochemistry. Bronchial thickness and the collagen/elastic fibers density were evaluated by morphometry. We measured the mean linear intercept (Lm), a measure of alveolar distension, and the mean airspace diameter (D0) and statistical distribution (D2). Results: DEP decreased IFN-gamma levels in BAL (p = 0.03), but did not significantly alter IL-4, IL-10 and IL-13 levels. MAC2+ macrophage, CD4+ T cell and CD20+ B cell numbers were not altered; however, numbers of CD3+ T cells (p <= 0.001) and CD8+ T cells (p <= 0.001) increased in the parenchyma. Although IL-13 (p = 0.008) expression decreased in the bronchiolar epithelium, Muc5ac gene expression was not altered in the lung of DEP-exposed animals. Although respiratory mechanics, elastic and collagen density were not modified, the mean linear intercept (Lm) was increased in the DEP-exposed animals (p <= 0.001), and the index D2 was statistically different (p = 0.038) from the control animals. Conclusion: Our data suggest that nasal instillation of low doses of DEP over a period of 90 days results in alveolar enlargement in the pulmonary parenchyma of healthy mice.
- The effects of particulate matter on inflammation of respiratory system: Differences between male and female(2017) YOSHIZAKI, Kelly; BRITO, Jose Mara; SILVA, Luiz Fernando; LINO-DOS-SANTOS-FRANCO, Adriana; FRIAS, Daniela Perroni; SILVA, Renata Calciolari Rossi e; AMATO-LOURENCO, Luis Fernando; SALDIVA, Paulo Hilario Nascimento; TIBERIO, Iolanda de Fatima Lopes Calvo; MAUAD, Thais; MACCHIONE, MariangelaAir pollution is known to exacerbate respiratory diseases and epidemiological studies have shown that women present more chronic respiratory symptoms than man exposed to traffic pollution, however, the reason why is unclear. This study evaluated the inflammatory differences in BALB/c mouse males (n = 34) and females (n = 111) in three phases of the estrous cycle that were exposed to ambient air (AA) or concentrated ambient particles (CAPs). Tracheal hyperreactivity to methacholine, bronchoalveolar lavage fluid (BALF) and immunohistochemical of airways and lung parenchyma were studied. Hyperreactivity increased in CAPs-exposed female mice compared with AA-exposed mice in estrus (p < 0.05) and proestrus phases (p < 0.05) and decreased in CAPs-exposed males compared with those exposed to AA (p < 0.05). Males had increased numbers of total cells (p = 0.037) and macrophages (p = 0.028) compared to females. BALF levels of cyclooxygenase-2(COX-2) (p = 0.000), transforming growth factor alpha (TGF-alpha) (p = 0.001) and IL-8 receptor alpha (IL-8R alpha) (p = 0.014) were increased in males compared with proestrus, estrus and diestrus females, independent of exposure. Proestrus females exhibited significantly higher cadherin expression in lung parenchyma than did males (p = 0.005). CAPs exposure increased matrix metalloproteinase-9 (MMP-9) (p = 0.024) and isoprostane (p = 0.003) expression in the airways of both, males and females. The level of substance P (SP) (p = 0.001) increased in lung parenchyma in males compared with females, while IL-17 levels in airways (p = 0.042) and in lung parenchyma (p = 0.008) increased in females. MMP-9 levels (p = 0.024) were significantly lower in the lung parenchyma of CAPs-exposed females. TGF-alpha (p = 0.007) levels increased in the lung parenchyma of CAPs-exposed females compared to AA-exposed females. These results suggest that inflammatory markers differentially expressed in male mice were mostly linked to acute inflammation (IL-1 beta, IL-8R alpha, COX-2), whereas in females, markers that may lead to a chronic inflammatory process such as IL-17 and remodeling (MMP-9) were increased.
conferenceObject Inhalation of exhaust particles of biodiesel fuel promotes similar alterations on heart rate variability induced by diesel fuel(2014) MACCHIONE, Mariangela; BRITO, Jose Mara; CAVALHEIRO, Guilherme; YOSHIZAKI, Kelly; GUIMARAES, Eliane; LICHTENFELS, Ana Julia; ANDRE, Paulo; RIVERO, Dolores; SALDIVA, Paulo