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| Author(s): |
Alyne Riani Moreira
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2018-10-31 |
| Examining board members: |
Fernanda Degobbi Tenorio Quirino dos Santos Lopes;
Renato Fraga Righetti;
Rodolfo de Paula Vieira
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| Advisor: | Fernanda Degobbi Tenorio Quirino dos Santos Lopes |
| Abstract | |
BACKGROUND: Macrophages are cells involved on progression of pulmonary emphysema and may assume different functions depending on microenvironment. stimuli. In presence of Interferon-? (IFN-y) occurs the polarization of macrophages M1, recognized as pro-inflammatory. However, in presence of interleukins-4 (IL-4) and -13 (IL-13), there is an alternative polarization of M2-type macrophages, recognized as anti-inflammatory action and good phagocytic action for microorganisms and apoptotic cells. Considering that the progression of emphysema is associated with the reduction of eferocytosis activity and that the pulmonary response on presence of pollutants depends on the effective action of the macrophages to eliminate these particles. AIM: To perform a temporal analysis of inflammation progression mediated by immune verify the participation of the different macrophages phenotypes involved in the process development of emphysema in mice submitted to pollutants. METHODS: C57BL/6 mice received intranasal instillation of elastase for emphysema induction on control groups received saline and exposed to polluted or filtered air for 60 days according to the groups. We evaluated respiratory mechanics, elastic and collagen fibers and in the amounts of Caspase 3 positive cells and inflammatory profile in BAL and evaluation of the mean linear intercept, we also evaluated the expression of IL-12, TNF-alpha, IFN-y, IL-4, IL-10 and IL-13 cytokines by ELISA in lung homogenate. RESULTS: The SAL + POL and PPE + AF groups showed an increase in alveolar intelect enhancement, macrophages, lymphocytes and epithelial cells in BAL, and in elastic and collagen fibers and in the amounts of Caspase 3 positive cells and these responses were exacerbated in animals receiving PPE and were exposed to diesel exhausted particles. The analysis of respiratory mechanics revealed a decrease in tissue elastance and tissue damping only in the PPE groups, whereas IL-4, IL-10 and IL-13 expression was increased only in the groups exposed to pollution. RT-PCR and flow cytometry showed an increase for the M2 phenotypic markers in the PPE + AF and SAL + POL groups and these responses were exacerbated in the PPE + POL group. CONCLUSION: The association between PPE instillation and diesel exposure exacerbated the inflammatory response and emphysema in mice. In addition, only exposure to particulate pollutants exhausted from diesel burning has already induced an inflammatory response with the development of emphysema even at concentrations that are in line with international ambient air quality standards. Both factors induced a polarization of the M2 phenotype, probably due to the high demand for phagocytosis of apoptotic cells (AU) | |
| FAPESP's process: | 15/19751-1 - A study of macrophages M1 and M2 in the progression of emphysema in animals exposed to fine particulate matter (PM 2.5) from diesel exhaust |
| Grantee: | Alyne Riani Moreira |
| Support Opportunities: | Scholarships in Brazil - Master |