Respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness

Exposure to chlorine (Cl2) damages airway and alveolar epithelia resulting in acute lung injury and reactive airway hyperresponsiveness (AHR) to methacholine. However, little is known about the effect of preexisting respiratory disease on Cl2-induced lung injury. By using a murine respiratory syncytial virus (RSV) infection model, we found that preexisting RSV infection increases Cl2 (187 ppm for 30 min)-induced lung inflammation and airway AHR at 24 h after exposure (5 days after infection). RSV infection and Cl2 exposure synergistically induced oxygen desaturation and neutrophil infiltration and increased MCP-1, MIP-1β, IL-10, IFN-γ, and RANTES concentrations in the bronchoalveolar lavage fluid (BALF). In contrast, levels of type 2 cytokines (i.e., IL-4, IL-5, IL-9, and IL-13) were not significantly affected by either RSV infection or Cl2 exposure. Cl2 exposure, but not RSV infection, induced AHR to methacholine challenge as measured by flexiVent. Moreover, preexisting RSV infection amplified BALF levels of hyaluronan (HA) and AHR. The Cl2-induced AHR was mitigated by treatment with inter-α-trypsin inhibitor antibody, which inhibits HA signaling, suggesting a mechanism of HA-mediated AHR from exacerbated oxidative injury. Our results show for the first time that preexisting RSV infection predisposes the lung to Cl2-induced injury. These data emphasize the necessity for further research on the effects of Cl2 in vulnerable populations and the development of appropriate treatments..

Medienart:

Artikel

Erscheinungsjahr:

2015

Erschienen:

2015

Enthalten in:

Zur Gesamtaufnahme - volume:309

Enthalten in:

American journal of physiology / Lung cellular and molecular physiology - 309(2015), 3, Seite L205

Sprache:

Englisch

Beteiligte Personen:

Song, Weifeng [VerfasserIn]
Yu, Zhihong [Sonstige Person]
Doran, Stephen F [Sonstige Person]
Ambalavanan, Namasivayam [Sonstige Person]
Steele, Chad [Sonstige Person]
Garantziotis, Stavros [Sonstige Person]
Matalon, Sadis [Sonstige Person]

Links:

Volltext
www.ncbi.nlm.nih.gov
search.proquest.com

BKL:

44.00

42.00

Themen:

Acute Lung Injury - chemically induced
Acute Lung Injury - immunology
Acute Lung Injury - virology
Air Pollutants - toxicity
Chemokines - metabolism
Chlorine
Chlorine - toxicity
Cytokines
Health aspects
Hyaluronic Acid - metabolism
Hyaluronic acid
Inflammatory diseases
Lung diseases
Physiology
Respiratory Hypersensitivity - chemically induced
Respiratory Hypersensitivity - immunology
Respiratory Hypersensitivity - virology
Respiratory Syncytial Virus Infections - immunology
Respiratory syncytial virus
Signal transduction
Viral infections
Virus diseases

doi:

10.1152/ajplung.00159.2015

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC1968378324