Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Instillation of hyaluronan reverses acid instillation injury to the mammalian blood gas barrier.

Authors: Zhou, Ting; Yu, Zhihong; Jian, Ming-Yuan; Ahmad, Israr; Trempus, Carol; Wagener, Brant M; Pittet, Jean-Francois; Aggarwal, Saurabh; Garantziotis, Stavros; Song, Weifeng; Matalon, Sadis

Published In Am J Physiol Lung Cell Mol Physiol, (2018 05 01)

Abstract: Acid (HCl) aspiration during anesthesia may lead to acute lung injury. There is no effective therapy. We hypothesized that HCl instilled intratracheally in C57BL/6 mice results in the formation of low-molecular weight hyaluronan (L-HA), which activates RhoA and Rho kinase (ROCK), causing airway hyperresponsiveness (AHR) and increased permeability. Furthermore, instillation of high-molecular weight hyaluronan (H-HA; Yabro) will reverse lung injury. We instilled HCl in C57BL/6 wild-type (WT), myeloperoxidase gene-deficient (MPO-/-) mice, and CD44 gene-deficient (CD44-/-) mice. WT mice were also instilled intranasally with H-HA (Yabro) at 1 and 23 h post-HCl. All measurements were performed at 1, 5, or 24 h post-HCl. Instillation of HCl in WT but not in CD44-/- resulted in increased inflammation, AHR, lung injury, and L-HA in the bronchoalveolar lavage fluid (BALF) 24 h post-HCl; L-HA levels and lung injury were significantly lower in HCl-instilled MPO-/- mice. Isolated perfused lungs of HCl instilled WT but not of CD44-/- mice had elevated values of the filtration coefficient ( Kf). Addition of L-HA on the apical surface of human primary bronchial epithelial cell monolayer decreased barrier resistance ( RT). H-HA significantly mitigated inflammation, AHR, and pulmonary vascular leakage at 24 h after HCl instillation and mitigated the increase of Kf and RT, as well as ROCK2 phosphorylation. Increased H- and L-HA levels were found in the BALF of mechanically ventilated patients but not in healthy volunteers. HCl instillation-induced lung injury is mediated by the L-HA-CD44-RhoA-ROCK2 signaling pathway, and H-HA is a potential novel therapeutic agent for acid aspiration-induced lung injury.

PubMed ID: 29368549 Exiting the NIEHS site

MeSH Terms: Acute Lung Injury/chemically induced; Acute Lung Injury/drug therapy*; Acute Lung Injury/metabolism; Acute Lung Injury/pathology; Animals; Blood-Air Barrier/drug effects*; Blood-Air Barrier/metabolism; Blood-Air Barrier/pathology; Bronchoalveolar Lavage Fluid/chemistry; Cells, Cultured; Humans; Hyaluronan Receptors/physiology*; Hyaluronic Acid/pharmacology*; Hydrochloric Acid/toxicity*; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Peroxidase/physiology*; Pneumonia/chemically induced; Pneumonia/drug therapy*; Pneumonia/metabolism; Pneumonia/pathology; Pulmonary Gas Exchange; Viscosupplements/pharmacology

Back
to Top