UMMS Affiliation

Division of Infectious Diseases and Immunology, Department of Medicine

Publication Date


Document Type



Immunology and Infectious Disease | Respiratory Tract Diseases


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.


arginase 1, cholesterol ester transfer protein, chronic obstructive pulmonary disease, inflammation, interleukin-10, macrophage—cell, pulmonary emphysema

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Copyright © 2021 Santana, Righetti, Breda, Domínguez-Amorocho, Ramalho, Dantas, Nunes, Tibério, Soriano, Câmara, Quintão and Cazita. 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.

DOI of Published Version



Santana KG, Righetti RF, Breda CNS, Domínguez-Amorocho OA, Ramalho T, Dantas FEB, Nunes VS, Tibério IFLC, Soriano FG, Câmara NOS, Quintão ECR, Cazita PM. Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema. Front Immunol. 2021 Jul 21;12:684076. doi: 10.3389/fimmu.2021.684076. PMID: 34367144; PMCID: PMC8334866. Link to article on publisher's site

Journal/Book/Conference Title

Frontiers in immunology

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PubMed ID


Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.