By activating endothelium histone H4 mediates oleic acid-induced acute respiratory distress syndrome
Abstract Objective This study investigated pathogenic role and mechanism of extracellular histone H4 during oleic acid (OA)-induced acute respiratory distress syndrome (ARDS). Methods: ARDS was induced by intravenous injection of OA in mice, and evaluated by blood gas, pathological analysis, lung ed...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | BMC Pulmonary Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12890-024-03334-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544984840372224 |
|---|---|
| author | Yanlin Zhang Jingjin Tan Yiran Zhao Li Guan Shuqiang Li |
| author_facet | Yanlin Zhang Jingjin Tan Yiran Zhao Li Guan Shuqiang Li |
| author_sort | Yanlin Zhang |
| collection | DOAJ |
| description | Abstract Objective This study investigated pathogenic role and mechanism of extracellular histone H4 during oleic acid (OA)-induced acute respiratory distress syndrome (ARDS). Methods: ARDS was induced by intravenous injection of OA in mice, and evaluated by blood gas, pathological analysis, lung edema, and survival rate. Heparan sulfate (HS) degradation was evaluated using immunofluorescence and flow cytometry. The released von Willebrand factor (vWF) was measured using ELISA. P-selectin translocation and neutrophil infiltration were measured via immunohistochemical analysis. Changes in VE-cadherin were measured by western blot. Blocking antibodies against TLRs were used to investigate the signaling pathway. Results: Histone H4 in plasma and BALF increased significantly after OA injection. Histone H4 was closely correlated with the OA dose, which determined the ARDS severity. Pretreatment with histone H4 further aggravated pulmonary edema and death rate, while anti-H4 antibody exerted obvious protective effects. Histone H4 directly activated the endothelia. Endothelial activation was evidently manifested as HS degradation, release of vWF, P-selectin translocation, and VE-Cadherin reduction. The synergistic stimulus of activated endothelia was required for effective neutrophil activation by histone H4. Both TLRs and calcium mediated histone H4-induced endothelial activation. Conclusions: Histone H4 is a pro-inflammatory and pro-thrombotic molecule in OA-induced ARDS in mice. |
| format | Article |
| id | doaj-art-8ad0fa7ab8f441faaf0d0a9c3b11e329 |
| institution | Kabale University |
| issn | 1471-2466 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pulmonary Medicine |
| spelling | doaj-art-8ad0fa7ab8f441faaf0d0a9c3b11e3292025-01-12T12:06:36ZengBMCBMC Pulmonary Medicine1471-24662025-01-0125111210.1186/s12890-024-03334-wBy activating endothelium histone H4 mediates oleic acid-induced acute respiratory distress syndromeYanlin Zhang0Jingjin Tan1Yiran Zhao2Li Guan3Shuqiang Li4Research Center of Occupational Medicine, Peking University Third HospitalResearch Center of Occupational Medicine, Peking University Third HospitalResearch Center of Occupational Medicine, Peking University Third HospitalResearch Center of Occupational Medicine, Peking University Third HospitalResearch Center of Occupational Medicine, Peking University Third HospitalAbstract Objective This study investigated pathogenic role and mechanism of extracellular histone H4 during oleic acid (OA)-induced acute respiratory distress syndrome (ARDS). Methods: ARDS was induced by intravenous injection of OA in mice, and evaluated by blood gas, pathological analysis, lung edema, and survival rate. Heparan sulfate (HS) degradation was evaluated using immunofluorescence and flow cytometry. The released von Willebrand factor (vWF) was measured using ELISA. P-selectin translocation and neutrophil infiltration were measured via immunohistochemical analysis. Changes in VE-cadherin were measured by western blot. Blocking antibodies against TLRs were used to investigate the signaling pathway. Results: Histone H4 in plasma and BALF increased significantly after OA injection. Histone H4 was closely correlated with the OA dose, which determined the ARDS severity. Pretreatment with histone H4 further aggravated pulmonary edema and death rate, while anti-H4 antibody exerted obvious protective effects. Histone H4 directly activated the endothelia. Endothelial activation was evidently manifested as HS degradation, release of vWF, P-selectin translocation, and VE-Cadherin reduction. The synergistic stimulus of activated endothelia was required for effective neutrophil activation by histone H4. Both TLRs and calcium mediated histone H4-induced endothelial activation. Conclusions: Histone H4 is a pro-inflammatory and pro-thrombotic molecule in OA-induced ARDS in mice.https://doi.org/10.1186/s12890-024-03334-wAcute respiratory distress syndromePulmonary fat embolismOleic acidExtracellular histone H4Pulmonary endothelium |
| spellingShingle | Yanlin Zhang Jingjin Tan Yiran Zhao Li Guan Shuqiang Li By activating endothelium histone H4 mediates oleic acid-induced acute respiratory distress syndrome BMC Pulmonary Medicine Acute respiratory distress syndrome Pulmonary fat embolism Oleic acid Extracellular histone H4 Pulmonary endothelium |
| title | By activating endothelium histone H4 mediates oleic acid-induced acute respiratory distress syndrome |
| title_full | By activating endothelium histone H4 mediates oleic acid-induced acute respiratory distress syndrome |
| title_fullStr | By activating endothelium histone H4 mediates oleic acid-induced acute respiratory distress syndrome |
| title_full_unstemmed | By activating endothelium histone H4 mediates oleic acid-induced acute respiratory distress syndrome |
| title_short | By activating endothelium histone H4 mediates oleic acid-induced acute respiratory distress syndrome |
| title_sort | by activating endothelium histone h4 mediates oleic acid induced acute respiratory distress syndrome |
| topic | Acute respiratory distress syndrome Pulmonary fat embolism Oleic acid Extracellular histone H4 Pulmonary endothelium |
| url | https://doi.org/10.1186/s12890-024-03334-w |
| work_keys_str_mv | AT yanlinzhang byactivatingendotheliumhistoneh4mediatesoleicacidinducedacuterespiratorydistresssyndrome AT jingjintan byactivatingendotheliumhistoneh4mediatesoleicacidinducedacuterespiratorydistresssyndrome AT yiranzhao byactivatingendotheliumhistoneh4mediatesoleicacidinducedacuterespiratorydistresssyndrome AT liguan byactivatingendotheliumhistoneh4mediatesoleicacidinducedacuterespiratorydistresssyndrome AT shuqiangli byactivatingendotheliumhistoneh4mediatesoleicacidinducedacuterespiratorydistresssyndrome |