Neutrophil depletion suppresses pulmonary vascular hyperpermeability and occurrence of pulmonary edema caused by hantavirus infection in C.B-17 SCID mice.
Hantavirus infections are characterized by vascular hyperpermeability and neutrophilia. However, the pathogenesis of this disease is poorly understood. Here, we demonstrate for the first time that pulmonary vascular permeability is increased by Hantaan virus infection and results in the development of pulmonary edema in C.B-17 severe combined immunodeficiency (SCID) mice lacking functional T cells and B cells. Increases in neutrophils in the lung and blood were observed when pulmonary edema began to be observed in the infected SCID mice. The occurrence of pulmonary edema was inhibited by neutrophil depletion. Moreover, the pulmonary vascular permeability was also significantly suppressed by neutrophil depletion in the infected mice. Taken together, the results suggest that neutrophils play an important role in pulmonary vascular hyperpermeability and the occurrence of pulmonary edema after hantavirus infection in SCID mice.


OBJECTIVE
Although hantavirus infections are characterized by the occurrence of pulmonary edema, the pathogenic mechanism remains largely unknown. In this study, we demonstrated for the first time in vivo that hantavirus infection increases pulmonary vascular permeability and results in the development of pulmonary edema in SCID mice. This novel mouse model for human hantavirus infection will be a valuable tool and will contribute to elucidation of the pathogenetic mechanisms. Although the involvement of neutrophils in the pathogenesis of hantavirus infection has largely been ignored, the results of this study using the mouse model suggest that neutrophils are involved in the vascular hyperpermeability and development of pulmonary edema in hantavirus infection. Further study of the mechanisms could lead to the development of specific treatment for hantavirus infection.
Department of Microbiology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Takaaki
T
Koma
Department of Microbiology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Kumiko
K
Yoshimatsu
Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
Noriyo
N
Nagata
Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
Yuko
Y
Sato
Department of Microbiology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Kenta
K
Shimizu
Department of Microbiology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Shumpei P
SP
Yasuda
Department of Microbiology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Takako
T
Amada
Department of Microbiology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Sanae
S
Nishio
Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
Hideki
H
Hasegawa
Department of Microbiology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan j_arika@med.hokudai.ac.jp.
Jiro
J
Arikawa
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D015153:Blotting, Western; D002199:Capillary Permeability / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006476:Orthohantavirus / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D018778:Hantavirus Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000276:immunology* / Q000821:virology; D051379:Mice; D016513:Mice, SCID / Q000821:virology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology
D012333:RNA, Messenger