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Extracellular Acetylated Histone 3.3 Induces Inflammation and Lung Tissue Damage

Extracellular histones, part of the protein group known as damage-associated molecular patterns (DAMPs), are released from damaged or dying cells and can instigate cellular toxicity. Within the context of chronic obstructive pulmonary disease (COPD), there is an observed abundance of extracellular h...

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Autores principales: Rico, Mario C., Perez-Leal, Oscar, Barbe, Mary F., Amin, Mamta, Colussi, Dennis J., Florez, Magda L., Olusajo, Victor, Rios, Dennise S., Barrero, Carlos A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527259/
https://www.ncbi.nlm.nih.gov/pubmed/37759735
http://dx.doi.org/10.3390/biom13091334
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author Rico, Mario C.
Perez-Leal, Oscar
Barbe, Mary F.
Amin, Mamta
Colussi, Dennis J.
Florez, Magda L.
Olusajo, Victor
Rios, Dennise S.
Barrero, Carlos A.
author_facet Rico, Mario C.
Perez-Leal, Oscar
Barbe, Mary F.
Amin, Mamta
Colussi, Dennis J.
Florez, Magda L.
Olusajo, Victor
Rios, Dennise S.
Barrero, Carlos A.
author_sort Rico, Mario C.
collection PubMed
description Extracellular histones, part of the protein group known as damage-associated molecular patterns (DAMPs), are released from damaged or dying cells and can instigate cellular toxicity. Within the context of chronic obstructive pulmonary disease (COPD), there is an observed abundance of extracellular histone H3.3, indicating potential pathogenic implications. Notably, histone H3.3 is often found hyperacetylated (AcH3.3) in the lungs of COPD patients. Despite these observations, the specific role of these acetylated histones in inducing pulmonary tissue damage in COPD remains unclear. To investigate AcH3.3’s impact on lung tissue, we administered recombinant histones (rH2A, rH3.3, and rAcH3.3) or vehicle solution to mice via intratracheal instillation. After 48 h, we evaluated the lung toxicity damage and found that the rAcH3.3 treated animals exhibited more severe lung tissue damage compared to those treated with non-acetylated H3.3 and controls. The rAcH3.3 instillation resulted in significant histological changes, including alveolar wall rupture, epithelial cell damage, and immune cell infiltration. Micro-CT analysis confirmed macroscopic structural changes. The rAcH3.3 instillation also increased apoptotic activity (cleavage of caspase 3 and 9) and triggered acute systemic inflammatory marker activation (TNF-α, IL-6, MCP-3, or CXCL-1) in plasma, accompanied by leukocytosis and lymphocytosis. Confocal imaging analysis confirmed lymphocytic and monocytic/macrophage lung infiltration in response to H3.3 and AcH3.3 administration. Taken together, our findings implicate extracellular AcH3.3 in inducing cytotoxicity and acute inflammatory responses, suggesting its potential role in promoting COPD-related lung damage progression.
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spelling pubmed-105272592023-09-28 Extracellular Acetylated Histone 3.3 Induces Inflammation and Lung Tissue Damage Rico, Mario C. Perez-Leal, Oscar Barbe, Mary F. Amin, Mamta Colussi, Dennis J. Florez, Magda L. Olusajo, Victor Rios, Dennise S. Barrero, Carlos A. Biomolecules Article Extracellular histones, part of the protein group known as damage-associated molecular patterns (DAMPs), are released from damaged or dying cells and can instigate cellular toxicity. Within the context of chronic obstructive pulmonary disease (COPD), there is an observed abundance of extracellular histone H3.3, indicating potential pathogenic implications. Notably, histone H3.3 is often found hyperacetylated (AcH3.3) in the lungs of COPD patients. Despite these observations, the specific role of these acetylated histones in inducing pulmonary tissue damage in COPD remains unclear. To investigate AcH3.3’s impact on lung tissue, we administered recombinant histones (rH2A, rH3.3, and rAcH3.3) or vehicle solution to mice via intratracheal instillation. After 48 h, we evaluated the lung toxicity damage and found that the rAcH3.3 treated animals exhibited more severe lung tissue damage compared to those treated with non-acetylated H3.3 and controls. The rAcH3.3 instillation resulted in significant histological changes, including alveolar wall rupture, epithelial cell damage, and immune cell infiltration. Micro-CT analysis confirmed macroscopic structural changes. The rAcH3.3 instillation also increased apoptotic activity (cleavage of caspase 3 and 9) and triggered acute systemic inflammatory marker activation (TNF-α, IL-6, MCP-3, or CXCL-1) in plasma, accompanied by leukocytosis and lymphocytosis. Confocal imaging analysis confirmed lymphocytic and monocytic/macrophage lung infiltration in response to H3.3 and AcH3.3 administration. Taken together, our findings implicate extracellular AcH3.3 in inducing cytotoxicity and acute inflammatory responses, suggesting its potential role in promoting COPD-related lung damage progression. MDPI 2023-08-31 /pmc/articles/PMC10527259/ /pubmed/37759735 http://dx.doi.org/10.3390/biom13091334 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rico, Mario C.
Perez-Leal, Oscar
Barbe, Mary F.
Amin, Mamta
Colussi, Dennis J.
Florez, Magda L.
Olusajo, Victor
Rios, Dennise S.
Barrero, Carlos A.
Extracellular Acetylated Histone 3.3 Induces Inflammation and Lung Tissue Damage
title Extracellular Acetylated Histone 3.3 Induces Inflammation and Lung Tissue Damage
title_full Extracellular Acetylated Histone 3.3 Induces Inflammation and Lung Tissue Damage
title_fullStr Extracellular Acetylated Histone 3.3 Induces Inflammation and Lung Tissue Damage
title_full_unstemmed Extracellular Acetylated Histone 3.3 Induces Inflammation and Lung Tissue Damage
title_short Extracellular Acetylated Histone 3.3 Induces Inflammation and Lung Tissue Damage
title_sort extracellular acetylated histone 3.3 induces inflammation and lung tissue damage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527259/
https://www.ncbi.nlm.nih.gov/pubmed/37759735
http://dx.doi.org/10.3390/biom13091334
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