Contribution of neutrophil-derived myeloperoxidase in the early phase of fulminant acute respiratory distress syndrome induced by influenza virus infection.
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.
Inflammation Program, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba-city, Chiba 260-8670, Japan.
Ryuichi
R
Sugamata
Hideki
H
Dobashi
Tomokazu
T
Nagao
Ki-Ichi
K
Yamamoto
Noriko
N
Nakajima
Yuko
Y
Sato
Yasuaki
Y
Aratani
Masamichi
M
Oshima
Tetsutaro
T
Sata
Kazuo
K
Kobayashi
Shoji
S
Kawachi
Toshinori
T
Nakayama
Kazuo
K
Suzuki
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005260:Female; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000473:pathology*; D009195:Peroxidase / Q000172:deficiency / Q000378:metabolism*; D011024:Pneumonia, Viral / Q000473:pathology; D012128:Respiratory Distress Syndrome / Q000473:pathology*
D016207:Cytokines; D009195:Peroxidase