Neutrophil Depletion Suppresses Pulmonary Vascular Hyperpermeability and Occurrence of Pulmonary Edema Caused by Hantavirus Infection in C.B-17 SCID Mice
Autor: | Kenta Shimizu, Shumpei P. Yasuda, Takaaki Koma, Takako Amada, Jiro Arikawa, Yuko Sato, Noriyo Nagata, Hideki Hasegawa, Kumiko Yoshimatsu, Sanae Nishio |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Orthohantavirus
Neutrophils Hantavirus Infections T-Lymphocytes Immunology Blotting Western Pulmonary Edema Mice SCID Biology Real-Time Polymerase Chain Reaction Microbiology Pathogenesis Capillary Permeability Immunoenzyme Techniques Mice In vivo Virology medicine Animals Humans RNA Messenger Lung Hantaan virus Cells Cultured Severe combined immunodeficiency B-Lymphocytes Reverse Transcriptase Polymerase Chain Reaction virus diseases Pulmonary edema medicine.disease Neutrophilia Disease Models Animal medicine.anatomical_structure Insect Science Pathogenesis and Immunity Female medicine.symptom Hantavirus Infection |
Popis: | 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. IMPORTANCE 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. |
Databáze: | OpenAIRE |
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