Therapeutic effects of high molecular weight hyaluronic acid in severe Pseudomonas aeruginosa pneumonia in ex vivo perfused human lungs
We previously reported that extracellular vesicles (EVs) released during Escherichia coli (E. coli) bacterial pneumonia were inflammatory, and administration of high molecular weight hyaluronic acid (HMW HA) suppressed several indices of acute lung injury (ALI) from E. coli pneumonia by binding to these inflammatory EVs. The current study was undertaken to study the therapeutic effects of HMW HA in ex vivo perfused human lungs injured with Pseudomonas aeruginosa (PA)103 bacterial pneumonia. For lungs with baseline alveolar fluid clearance (AFC) <10%/h, HMW HA 1 or 2 mg was injected intravenously after 1 h (n = 4-9), and EVs released during PA pneumonia were collected from the perfusate over 6 h. For lungs with baseline AFC > 10%/h, HMW HA 2 mg was injected intravenously after 1 h (n = 6). In vitro experiments were conducted to evaluate the effects of HA on inflammation and bacterial phagocytosis. For lungs with AFC < 10%/h, administration of HMW HA intravenously significantly restored AFC and numerically decreased protein permeability and alveolar inflammation from PA103 pneumonia but had no effect on bacterial counts at 6 h. However, HMW HA improved bacterial phagocytosis by human monocytes and neutrophils and suppressed the inflammatory properties of EVs released during pneumonia on monocytes. For lungs with AFC > 10%/h, administration of HMW HA intravenously improved AFC from PA103 pneumonia but had no significant effects on protein permeability, inflammation, or bacterial counts. In the presence of impaired alveolar epithelial transport capacity, administration of HMW HA improved the resolution of pulmonary edema from Pseudomonas PA103 bacterial pneumonia.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:321 |
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| Enthalten in: |
American journal of physiology. Lung cellular and molecular physiology - 321(2021), 5 vom: 01. Nov., Seite L827-L836 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Xiwen [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.11.2021 Date Revised 02.11.2022 published: Print-Electronic figshare: 10.6084/ m9.figshare.15161541, 10.6084/m9.figshare.13473450, 10.6084/m9.figshare.15161508, 10.6084/m9.figshare.15161517, 10.6084/m9.figshare.15161526, 10.6084/m9.figshare.15161529 Citation Status MEDLINE |
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| doi: |
10.1152/ajplung.00626.2020 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM330669206 |
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| 245 | 1 | 0 | |a Therapeutic effects of high molecular weight hyaluronic acid in severe Pseudomonas aeruginosa pneumonia in ex vivo perfused human lungs |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a We previously reported that extracellular vesicles (EVs) released during Escherichia coli (E. coli) bacterial pneumonia were inflammatory, and administration of high molecular weight hyaluronic acid (HMW HA) suppressed several indices of acute lung injury (ALI) from E. coli pneumonia by binding to these inflammatory EVs. The current study was undertaken to study the therapeutic effects of HMW HA in ex vivo perfused human lungs injured with Pseudomonas aeruginosa (PA)103 bacterial pneumonia. For lungs with baseline alveolar fluid clearance (AFC) <10%/h, HMW HA 1 or 2 mg was injected intravenously after 1 h (n = 4-9), and EVs released during PA pneumonia were collected from the perfusate over 6 h. For lungs with baseline AFC > 10%/h, HMW HA 2 mg was injected intravenously after 1 h (n = 6). In vitro experiments were conducted to evaluate the effects of HA on inflammation and bacterial phagocytosis. For lungs with AFC < 10%/h, administration of HMW HA intravenously significantly restored AFC and numerically decreased protein permeability and alveolar inflammation from PA103 pneumonia but had no effect on bacterial counts at 6 h. However, HMW HA improved bacterial phagocytosis by human monocytes and neutrophils and suppressed the inflammatory properties of EVs released during pneumonia on monocytes. For lungs with AFC > 10%/h, administration of HMW HA intravenously improved AFC from PA103 pneumonia but had no significant effects on protein permeability, inflammation, or bacterial counts. In the presence of impaired alveolar epithelial transport capacity, administration of HMW HA improved the resolution of pulmonary edema from Pseudomonas PA103 bacterial pneumonia | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Pseudomonas aeruginosa pneumonia | |
| 650 | 4 | |a acute lung injury | |
| 650 | 4 | |a alveolar fluid clearance | |
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| 650 | 4 | |a hyaluronic acid | |
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| 700 | 1 | |a Sugita, Shinji |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Airan |e verfasserin |4 aut | |
| 700 | 1 | |a Naito, Yoshifumi |e verfasserin |4 aut | |
| 700 | 1 | |a Hwang, Wonjung |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Haibo |e verfasserin |4 aut | |
| 700 | 1 | |a Sakamoto, Atsuhiro |e verfasserin |4 aut | |
| 700 | 1 | |a Sawa, Teiji |e verfasserin |4 aut | |
| 700 | 1 | |a Matthay, Michael A |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jae-Woo |e verfasserin |4 aut | |
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