Neutrophil Depletion Suppresses Pulmonary Vascular Hyperpermeability and Occurrence of Pulmonary Edema Caused by Hantavirus Infection in C.B-17 SCID Mice

Abstract

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. IMPORTANCEAlthough 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.

Lower Respiratory Tract Infection of the Ferret by 2009 H1N1 Pandemic Influenza A Virus Triggers Biphasic, Systemic, and Local Recruitment of Neutrophils

“…Previous studies have shown that neutrophils are capable of recognizing IAV and IAV-infected cells (91)(92)(93)(94), although discrepancies in data suggest that neutrophil responses to IAV are dependent on the viral strain (92)(93)(94)(95). Interest in the role of neutrophils in viral disease is quickly growing (56,(96)(97)(98), and the topic deserves further research.…”

Potent Antiedematous and Protective Effects of Ciprofloxacin in Pulmonary Ricinosis

“…Additionally, pulmonary hyperpermeability was significantly attenuated by ciprofloxacin, as exemplified by the finding that pulmonary extravasation of EBD was significantly lower in ricin-intoxicated mice treated with this drug. Since neutrophils play a crucial role in the development of pulmonary vascular hyperpermeability (28,29), attenuation of pulmonary neutrophil sequestration may play a role in the antiedematous effect observed. To elucidate additional mechanistic explanations of this potent antiedematous effect, we further looked for additional markers associated with vascular hyperpermeability.…”

Detection of Hantaan virus RNA from anti‐Hantaan virus IgG seronegative rodents in an area of high endemicity in Republic of Korea

“…For RT‐qPCR, cDNA synthesis was performed using a high capacity RNA‐to‐cDNA kit (Applied Biosystems) by adding 1 μg of total RNA from lung, liver, kidney or spleen. RT‐qPCR was performed using primers targeting the HTNV S segment with SYBR Green PCR Master mix (Applied Biosystems) on a StepOne Real‐Time PCR System (Applied Biosystems) .…”