2023 Fiscal Year Final Research Report
Does sST2 inhalation therapy ameliorate severe neutrophilic asthma? Analysis of neutrophil functions using intravital microscopy.
| Project/Area Number |
19KK0404
|
|---|
| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | Kyorin University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2020 – 2023
|
| Keywords | Asthma / Neutrophil / IL-33 / sST2 / ST2 / Intravital microscopy |
|---|
| Outline of Final Research Achievements |
In Japan, we embarked on an experiment, inhaling IL-33 and soluble ST2 in mice. To our surprise, soluble ST2 acted as a carrier protein for IL-33, significantly enhancing neutrophilic airway inflammation. We promptly reported this unexpected finding to the international journal.
In Canada, our focus was on analyzing neutrophil functions in live mice. In the Alternaria-induced neutrophilic asthma model, we observed an increase in the number and activity of neutrophils in the pulmonary microvasculature. Neutrophils were found to interact with platelets at a steady state, and this interaction was heightened in the neutrophil asthma model. However, the most surprising finding was the frequent migration of neutrophils between intra-microvascular spaces and alveoli, where they interacted with alveolar macrophages. This phenomenon was observed in both steady-state and neutrophilic asthma models, but the duration of the interaction was shorter in the neutrophilic asthma model.
|
| Free Research Field |
Asthma
|
| Academic Significance and Societal Importance of the Research Achievements |
sST2はヒトの肺内でIL-33と複合体を作り、好中球性気道炎症を増強する。IL-33-sST2複合体は炎症物質であり、治療ターゲットの候補である。
好中球性喘息モデルでは、血管内の好中球の数、移動性が増えている。好中球性喘息モデルでは血管内に好中球-血小板体複合体の数が増加した。アスピリン喘息患者では、この複合体がロイコトリエンを産生するため、この複合体が好中球性喘息の治療ターゲットの可能性がある。好中球が血管内と肺胞内の移動を繰り返し、マクロファージと相互作用することは、予想外の現象である。肺の恒常性維持のメカニズムの理解するうえで、パラダイムシフトを起こす可能性がある。
|
