Rico, M.C.; Perez-Leal, O.; Barbe, M.F.; Amin, M.; Colussi, D.J.; Florez, M.L.; Olusajo, V.; Barrero, C.A. Extracellular Histone 3.3 and Its Hyper-acetylated Isoform In-duce an Inflammatory Response and Damage Lung Tissue. Preprints2023, 2023051200. https://doi.org/10.20944/preprints202305.1200.v1
APA Style
Rico, M.C., Perez-Leal, O., Barbe, M.F., Amin, M., Colussi, D.J., Florez, M.L., Olusajo, V., & Barrero, C.A. (2023). Extracellular Histone 3.3 and Its Hyper-acetylated Isoform In-duce an Inflammatory Response and Damage Lung Tissue. Preprints. https://doi.org/10.20944/preprints202305.1200.v1
Chicago/Turabian Style
Rico, M.C., Victor Olusajo and Carlos A. Barrero. 2023 "Extracellular Histone 3.3 and Its Hyper-acetylated Isoform In-duce an Inflammatory Response and Damage Lung Tissue" Preprints. https://doi.org/10.20944/preprints202305.1200.v1
Abstract
Excessive extracellular histones can damage cells despite their importance in DNA structure and gene regulation. We previously showed the harmful effect of histone 3.3 (H3.3) and its acetylated form (AcH3.3) in chronic obstructive pulmonary disease (COPD), but further research is needed to understand the in vivo underlying mechanisms. To investigate this, we administered a single dose of recombinant histones via intra-tracheal instillation in C57BL/6 mice and analyzed the outcomes after 48 hours. Both rH3.3 and rAcH3.3 effectively reached the bronchial and alveolar space. Lung histology revealed severe immune cell infiltration, rupture, damage, and thickening of many alveolar walls. Micro-CT scans showed macroscopic structure changes with a decreased tissue volume to total volume ratio. The administration of rH3.3 and rAcH3.3 induced lung apoptotic activity, as indicated by increased levels of cleavage caspase 3 and 9. Moreover, elevated plasma levels of pro-inflammatory cell mediators, including TNF-alpha, IL-6, MCP-3, and CXCL-1, were observed. The pathological changes and pro-inflammatory cytokine response were more pronounced in animals treated with rAcH3.3, which also exhibited leukocytosis and lymphocytosis. These findings emphasize the crucial role of extracellular H3.3 acetylation in inducing cytotoxicity and a robust, acute inflammatory response similar to what occurs in the lungs of COPD patients.
Medicine and Pharmacology, Pulmonary and Respiratory Medicine
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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