tetano
Editor, Senior Moderator
Am J Respir Crit Care Med. 2012 Nov 9. [Epub ahead of print]
CXCL10-CXCR3 Enhances the Development of Neutrophil-mediated Fulminant Lung Injury of Viral and Non-viral Origin.
Ichikawa A, Kuba K, Morita M, Chida S, Tezuka H, Hara H, Sasaki T, Ohteki T, Ranieri VM, Dos Santos CC, Kawaoka Y, Akira S, Luster AD, Lu B, Penninger JM, Uhlig S, Slutsky AS, Imai Y.
Source
Akita University, Akita, Japan.
Abstract
RATIONALE:
Patients, who developed acute respiratory distress syndrome (ARDS) after infection with severe respiratory viruses (e.g.; SARS-corona virus, H5N1 avian influenza virus), exhibited unusually high levels of CXCL10 that belongs to the non-ELR CXC chemokine superfamily. CXCL10 may not be a bystander to the severe virus infection, but directly contribute to the pathogenesis of neutrophil-mediated, excessive pulmonary inflammation.
OBJECTIVES:
We investigated the contribution of CXCL10 and its receptor CXCR3 axis to the pathogenesis of ARDS with non-viral and viral origins.
METHODS:
We induced non-viral ARDS by acid aspiration and viral ARDS by intratracheal influenza virus infection, in wild-type mice and mice deficient with CXCL10, CXCR3, IFNAR1 (interferon [IFN]-α/β receptor 1), or TRIF.
MEASUREMENTS AND MAIN RESULTS:
We found that the mice lacking CXCL10 or CXCR3 demonstrated improved severity and survival of non-viral and viral ARDS, whereas mice that lack IFNAR1 did not control the severity of ARDS in vivo. The increased levels of CXCL10 in lungs with ARDS originate to a large extent from infiltrated pulmonary neutrophils, which express a unique CXCR3 receptor via TRIF. CXCL10-CXCR3 acts in an autocrine fashion on the oxidative burst and chemotaxis in the inflamed neutrophils, leading to fulminant pulmonary inflammation.
CONCLUSIONS:
CXCL10-CXCR3 signaling appears to be a critical factor for the exacerbation of the pathology of ARDS. Thus, CXCL10-CXCR3 axis could represent a prime therapeutic target in the treatment of acute phase of ARDS of non-viral and viral origins.
PMID:
23144331
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23144331
CXCL10-CXCR3 Enhances the Development of Neutrophil-mediated Fulminant Lung Injury of Viral and Non-viral Origin.
Ichikawa A, Kuba K, Morita M, Chida S, Tezuka H, Hara H, Sasaki T, Ohteki T, Ranieri VM, Dos Santos CC, Kawaoka Y, Akira S, Luster AD, Lu B, Penninger JM, Uhlig S, Slutsky AS, Imai Y.
Source
Akita University, Akita, Japan.
Abstract
RATIONALE:
Patients, who developed acute respiratory distress syndrome (ARDS) after infection with severe respiratory viruses (e.g.; SARS-corona virus, H5N1 avian influenza virus), exhibited unusually high levels of CXCL10 that belongs to the non-ELR CXC chemokine superfamily. CXCL10 may not be a bystander to the severe virus infection, but directly contribute to the pathogenesis of neutrophil-mediated, excessive pulmonary inflammation.
OBJECTIVES:
We investigated the contribution of CXCL10 and its receptor CXCR3 axis to the pathogenesis of ARDS with non-viral and viral origins.
METHODS:
We induced non-viral ARDS by acid aspiration and viral ARDS by intratracheal influenza virus infection, in wild-type mice and mice deficient with CXCL10, CXCR3, IFNAR1 (interferon [IFN]-α/β receptor 1), or TRIF.
MEASUREMENTS AND MAIN RESULTS:
We found that the mice lacking CXCL10 or CXCR3 demonstrated improved severity and survival of non-viral and viral ARDS, whereas mice that lack IFNAR1 did not control the severity of ARDS in vivo. The increased levels of CXCL10 in lungs with ARDS originate to a large extent from infiltrated pulmonary neutrophils, which express a unique CXCR3 receptor via TRIF. CXCL10-CXCR3 acts in an autocrine fashion on the oxidative burst and chemotaxis in the inflamed neutrophils, leading to fulminant pulmonary inflammation.
CONCLUSIONS:
CXCL10-CXCR3 signaling appears to be a critical factor for the exacerbation of the pathology of ARDS. Thus, CXCL10-CXCR3 axis could represent a prime therapeutic target in the treatment of acute phase of ARDS of non-viral and viral origins.
PMID:
23144331
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23144331