Hyaluronan mediates airway hyperresponsiveness in oxidative lung injury
Copyright © 2015 the American Physiological Society..
Chlorine (Cl2) inhalation induces severe oxidative lung injury and airway hyperresponsiveness (AHR) that lead to asthmalike symptoms. When inhaled, Cl2 reacts with epithelial lining fluid, forming by-products that damage hyaluronan, a constituent of the extracellular matrix, causing the release of low-molecular-weight fragments (L-HA, <300 kDa), which initiate a series of proinflammatory events. Cl2 (400 ppm, 30 min) exposure to mice caused an increase of L-HA and its binding partner, inter-α-trypsin-inhibitor (IαI), in the bronchoalveolar lavage fluid. Airway resistance following methacholine challenge was increased 24 h post-Cl2 exposure. Intratracheal administration of high-molecular-weight hyaluronan (H-HA) or an antibody against IαI post-Cl2 exposure decreased AHR. Exposure of human airway smooth muscle (HASM) cells to Cl2 (100 ppm, 10 min) or incubation with Cl2-exposed H-HA (which fragments it to L-HA) increased membrane potential depolarization, intracellular Ca(2+), and RhoA activation. Inhibition of RhoA, chelation of intracellular Ca(2+), blockade of cation channels, as well as postexposure addition of H-HA, reversed membrane depolarization in HASM cells. We propose a paradigm in which oxidative lung injury generates reactive species and L-HA that activates RhoA and Ca(2+) channels of airway smooth muscle cells, increasing their contractility and thus causing AHR.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:308 |
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| Enthalten in: |
American journal of physiology. Lung cellular and molecular physiology - 308(2015), 9 vom: 01. Mai, Seite L891-903 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lazrak, Ahmed [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.04.2016 Date Revised 17.03.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1152/ajplung.00377.2014 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2015 the American Physiological Society. | ||
| 520 | |a Chlorine (Cl2) inhalation induces severe oxidative lung injury and airway hyperresponsiveness (AHR) that lead to asthmalike symptoms. When inhaled, Cl2 reacts with epithelial lining fluid, forming by-products that damage hyaluronan, a constituent of the extracellular matrix, causing the release of low-molecular-weight fragments (L-HA, <300 kDa), which initiate a series of proinflammatory events. Cl2 (400 ppm, 30 min) exposure to mice caused an increase of L-HA and its binding partner, inter-α-trypsin-inhibitor (IαI), in the bronchoalveolar lavage fluid. Airway resistance following methacholine challenge was increased 24 h post-Cl2 exposure. Intratracheal administration of high-molecular-weight hyaluronan (H-HA) or an antibody against IαI post-Cl2 exposure decreased AHR. Exposure of human airway smooth muscle (HASM) cells to Cl2 (100 ppm, 10 min) or incubation with Cl2-exposed H-HA (which fragments it to L-HA) increased membrane potential depolarization, intracellular Ca(2+), and RhoA activation. Inhibition of RhoA, chelation of intracellular Ca(2+), blockade of cation channels, as well as postexposure addition of H-HA, reversed membrane depolarization in HASM cells. We propose a paradigm in which oxidative lung injury generates reactive species and L-HA that activates RhoA and Ca(2+) channels of airway smooth muscle cells, increasing their contractility and thus causing AHR | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Creighton, Judy |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Zhihong |e verfasserin |4 aut | |
| 700 | 1 | |a Komarova, Svetlana |e verfasserin |4 aut | |
| 700 | 1 | |a Doran, Stephen F |e verfasserin |4 aut | |
| 700 | 1 | |a Aggarwal, Saurabh |e verfasserin |4 aut | |
| 700 | 1 | |a Emala, Charles W |c Sr |e verfasserin |4 aut | |
| 700 | 1 | |a Stober, Vandy P |e verfasserin |4 aut | |
| 700 | 1 | |a Trempus, Carol S |e verfasserin |4 aut | |
| 700 | 1 | |a Garantziotis, Stavros |e verfasserin |4 aut | |
| 700 | 1 | |a Matalon, Sadis |e verfasserin |4 aut | |
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