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Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema
Cholesterol-ester transfer protein (CETP) plays a role in atherosclerosis, the inflammatory response to endotoxemia and in experimental and human sepsis. Functional alterations in lipoprotein (LP) metabolism and immune cell populations, including macrophages, occur during sepsis and may be related t...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8334866/ https://www.ncbi.nlm.nih.gov/pubmed/34367144 http://dx.doi.org/10.3389/fimmu.2021.684076 |
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author | Santana, Kelly Gomes Righetti, Renato Fraga Breda, Cristiane Naffah de Souza Domínguez-Amorocho, Omar Alberto Ramalho, Theresa Dantas, Francisca Elda B. Nunes, Valéria Sutti Tibério, Iolanda de Fátima Lopes Calvo Soriano, Francisco Garcia Câmara, Niels O. S. Quintão, Eder Carlos Rocha Cazita, Patrícia M. |
author_facet | Santana, Kelly Gomes Righetti, Renato Fraga Breda, Cristiane Naffah de Souza Domínguez-Amorocho, Omar Alberto Ramalho, Theresa Dantas, Francisca Elda B. Nunes, Valéria Sutti Tibério, Iolanda de Fátima Lopes Calvo Soriano, Francisco Garcia Câmara, Niels O. S. Quintão, Eder Carlos Rocha Cazita, Patrícia M. |
author_sort | Santana, Kelly Gomes |
collection | PubMed |
description | Cholesterol-ester transfer protein (CETP) plays a role in atherosclerosis, the inflammatory response to endotoxemia and in experimental and human sepsis. Functional alterations in lipoprotein (LP) metabolism and immune cell populations, including macrophages, occur during sepsis and may be related to comorbidities such as chronic obstructive pulmonary disease (COPD). Macrophages are significantly associated with pulmonary emphysema, and depending on the microenvironment, might exhibit an M1 or M2 phenotype. Macrophages derived from the peritoneum and bone marrow reveal CETP that contributes to its plasma concentration. Here, we evaluated the role of CETP in macrophage polarization and elastase-induced pulmonary emphysema (ELA) in human CETP-expressing transgenic (huCETP) (line 5203, C57BL6/J background) male mice and compared it to their wild type littermates. We showed that bone marrow-derived macrophages from huCETP mice reduce polarization toward the M1 phenotype, but with increased IL-10. Compared to WT, huCETP mice exposed to elastase showed worsened lung function with an increased mean linear intercept (Lm), reflecting airspace enlargement resulting from parenchymal destruction with increased expression of arginase-1 and IL-10, which are M2 markers. The cytokine profile revealed increased IL-6 in plasma and TNF, and IL-10 in bronchoalveolar lavage (BAL), corroborating with the lung immunohistochemistry in the huCETP-ELA group compared to WT-ELA. Elastase treatment in the huCETP group increased VLDL-C and reduced HDL-C. Elastase-induced pulmonary emphysema in huCETP mice promotes lung M2-like phenotype with a deleterious effect in experimental COPD, corroborating the in vitro result in which CETP promoted M2 macrophage polarization. Our results suggest that CETP is associated with inflammatory response and influences the role of macrophages in COPD. |
format | Online Article Text |
id | pubmed-8334866 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83348662021-08-05 Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema Santana, Kelly Gomes Righetti, Renato Fraga Breda, Cristiane Naffah de Souza Domínguez-Amorocho, Omar Alberto Ramalho, Theresa Dantas, Francisca Elda B. Nunes, Valéria Sutti Tibério, Iolanda de Fátima Lopes Calvo Soriano, Francisco Garcia Câmara, Niels O. S. Quintão, Eder Carlos Rocha Cazita, Patrícia M. Front Immunol Immunology Cholesterol-ester transfer protein (CETP) plays a role in atherosclerosis, the inflammatory response to endotoxemia and in experimental and human sepsis. Functional alterations in lipoprotein (LP) metabolism and immune cell populations, including macrophages, occur during sepsis and may be related to comorbidities such as chronic obstructive pulmonary disease (COPD). Macrophages are significantly associated with pulmonary emphysema, and depending on the microenvironment, might exhibit an M1 or M2 phenotype. Macrophages derived from the peritoneum and bone marrow reveal CETP that contributes to its plasma concentration. Here, we evaluated the role of CETP in macrophage polarization and elastase-induced pulmonary emphysema (ELA) in human CETP-expressing transgenic (huCETP) (line 5203, C57BL6/J background) male mice and compared it to their wild type littermates. We showed that bone marrow-derived macrophages from huCETP mice reduce polarization toward the M1 phenotype, but with increased IL-10. Compared to WT, huCETP mice exposed to elastase showed worsened lung function with an increased mean linear intercept (Lm), reflecting airspace enlargement resulting from parenchymal destruction with increased expression of arginase-1 and IL-10, which are M2 markers. The cytokine profile revealed increased IL-6 in plasma and TNF, and IL-10 in bronchoalveolar lavage (BAL), corroborating with the lung immunohistochemistry in the huCETP-ELA group compared to WT-ELA. Elastase treatment in the huCETP group increased VLDL-C and reduced HDL-C. Elastase-induced pulmonary emphysema in huCETP mice promotes lung M2-like phenotype with a deleterious effect in experimental COPD, corroborating the in vitro result in which CETP promoted M2 macrophage polarization. Our results suggest that CETP is associated with inflammatory response and influences the role of macrophages in COPD. Frontiers Media S.A. 2021-07-21 /pmc/articles/PMC8334866/ /pubmed/34367144 http://dx.doi.org/10.3389/fimmu.2021.684076 Text en Copyright © 2021 Santana, Righetti, Breda, Domínguez-Amorocho, Ramalho, Dantas, Nunes, Tibério, Soriano, Câmara, Quintão and Cazita https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Santana, Kelly Gomes Righetti, Renato Fraga Breda, Cristiane Naffah de Souza Domínguez-Amorocho, Omar Alberto Ramalho, Theresa Dantas, Francisca Elda B. Nunes, Valéria Sutti Tibério, Iolanda de Fátima Lopes Calvo Soriano, Francisco Garcia Câmara, Niels O. S. Quintão, Eder Carlos Rocha Cazita, Patrícia M. Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema |
title | Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema |
title_full | Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema |
title_fullStr | Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema |
title_full_unstemmed | Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema |
title_short | Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema |
title_sort | cholesterol-ester transfer protein alters m1 and m2 macrophage polarization and worsens experimental elastase-induced pulmonary emphysema |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8334866/ https://www.ncbi.nlm.nih.gov/pubmed/34367144 http://dx.doi.org/10.3389/fimmu.2021.684076 |
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