Contribution of neutrophil-derived myeloperoxidase in the early phase of fulminant acute respiratory distress syndrome induced by influenza virus infection.

Abstract

Because the pathogenesis of acute respiratory distress syndrome (ARDS) induced by influenza virus infection remains unknown, we can only improve on existing therapeutic interventions. To approach the subject, we investigated immunological etiology focused on cytokines and an acute lung damage factor in influenza-induced ARDS by using a PR-8 (A/H1N1)-infected mouse model. The infected mouse showed fulminant severe pneumonia with leukocyte infiltration, claudin alteration on tight junctions, and formation of hyaline membranes. In addition to interferon (IFN)-α, plenty of keratinocyte-derived chemokines (KC), macrophage inflammatory protein 2 (MIP-2), regulated on activation normal T-cell expressed and secreted (RANTES), and monocyte chemotactic protein 1 (MCP-1) were significantly released into bronchoalveolar lavage fluid (BALF) of the model. We focused on neutrophil myeloperoxidase (MPO) as a potent tissue damage factor and examined its contribution in influenza pneumonia by using mice genetically lacking in MPO. The absence of MPO reduced inflammatory damage with suppression of leakage of total BALF proteins associated with alteration of claudins in the lung. MPO(-/-) mice also suppressed viral load in the lung. The present study suggests that MPO-mediated OCl(-) generation affects claudin molecules and leads to protein leakage and viral spread as a damage factor in influenza-induced ARDS.

• Authors: Ryuichi Sugamata, Hideki Dobashi, Tomokazu Nagao, Ki-Ichi Yamamoto, Noriko Nakajima, Yuko Sato, Yasuaki Aratani, Masamichi Oshima, Tetsutaro Sata, Kazuo Kobayashi, Shoji Kawachi, Toshinori Nakayama, Kazuo Suzuki
• Journal: Microbiology and immunology (Microbiol Immunol) Vol. 56 Issue 3 Pg. 171-82 (Mar 2012) ISSN: 1348-0421 [Electronic] Australia
• PMID: 22211924 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Societies and Blackwell Publishing Asia Pty Ltd.

Chemical References

• Cytokines
• Peroxidase

Topics

• Animals
• Cytokines (metabolism)
• Female
• Influenza A Virus, H1N1 Subtype (pathogenicity)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Neutrophils (immunology)
• Orthomyxoviridae Infections (pathology)
• Peroxidase (deficiency, metabolism)
• Pneumonia, Viral (pathology)
• Respiratory Distress Syndrome (pathology)