Basic Study of Lung Injuries and Neutrophils - Isolation and Purification of Alveolus-Derived Neutrophil Inhibitory Factor and Its Effects on The Development of Lung Injuries -

肺损伤与中性粒细胞的基础研究 - 肺泡源性中性粒细胞抑制因子的分离纯化及其对肺损伤发展的影响 -

• 批准号: 10670531
• 负责人: SUWABE Akira
• 金额: $ 0.38万
• 依托单位: YAMAGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670531/
• 关键词: LUNG SURFACTANT; LUNG INJURY; NEUTROPHILS; SUPEROXIDES; ALVEOLAR TYPE II CELLS

Pulmonary surfactant and alveolar type II epithelial cells play important roles in lung defense mechanisms. We reported that native surfactant and its components (SP-A and phospholipid liposomes) as well as artificial surfactant (Surfactant-TA, S-TA) inhibited adherence, chemotaxis, release of superoxides and elastase of human peripheral neutrophils. Neutrophils reacted with S-TA showed characteristics of apoptotic cells. We also demonstrated that S-TA inhibited proliferation of rat lung fibroblasts and that S-TA protected a type II cell monolayer and enhanced its surfactant metabolism.Surfactant replacement therapy significantly decreases a mortality of ARDS patients. Surfactant may improve gas exchanges by preventing alveolar collapse. We showed that superoxide production from neutrophils obtained from the hamster lungs, in which S-TA was instilled 24 hours after bleomycin administration, was significantly inhibited, compared to neutrophils from control animals. The rats, which were replaced with S-TA twenty four hours and seven days after receiving bleomycin administration, showed a decrease in lung collagen content, compared to control animals. These findings suggest that S-TA may inhibit neutrophil activation or fibroblast proliferation and may protect type II cells from their damage.In summary, pulmonary surfactant was shown to have significant effects on functions of inflammatory cells, such as alveolar macrophages, lymphocytes, or neutrophils, as well as on those of stroma cells, such as fibroblasts or type II cells. Surfactant, together with type II celles, may be involved in the development of some kinds of pulmonary diseases. In the future aspects, development of new kinds of artificical surfactant as a therapeutic tool may be required, along with the studies on clinical usefulness and its mechanisms.

肺表面活性物质和肺泡II型上皮细胞在肺防御机制中起重要作用。本文报道了天然表面活性剂及其组分（SP-A和磷脂脂质体）和人工表面活性剂（Surfacing-TA、S-TA）对人外周血中性粒细胞粘附、趋化、释放超氧化物和弹性蛋白酶的抑制作用。中性粒细胞与S-TA反应呈凋亡细胞特征。S-TA可抑制大鼠肺成纤维细胞的增殖，保护肺Ⅱ型细胞单层，促进肺Ⅱ型细胞表面活性物质的代谢，并能显著降低ARDS患者的死亡率。表面活性剂可以通过防止肺泡萎陷来改善气体交换。我们发现，从仓鼠肺，其中S-TA滴注博来霉素给药后24小时，从中性粒细胞的超氧化物的生产，显着抑制，从对照动物的中性粒细胞相比。与对照动物相比，在接受博来霉素给药后24小时和7天用S-TA替代的大鼠显示肺胶原蛋白含量降低。这些结果表明，S-TA可以抑制中性粒细胞活化或成纤维细胞增殖，并可能保护II型细胞免受其损害。总之，肺表面活性物质被证明对炎症细胞的功能，如肺泡巨噬细胞，淋巴细胞，或中性粒细胞，以及对基质细胞，如成纤维细胞或II型细胞的功能有显着的影响。肺表面活性物质与II型细胞共同参与了某些肺部疾病的发生发展。在未来的方面，可能需要开发新型人工表面活性剂作为治疗工具，沿着对其临床用途及其机制进行研究。

项目成果

Akira Suwabe: "Artificial Surfactant (Surfactant TA) Modulates Adherence and Superoxide Production of Neutrophils"Am J Respir Crit Care Med. 158. 1890-1899 (1998)

Akira Suwabe：“人工表面活性剂（表面活性剂 TA）调节中性粒细胞的粘附和超氧化物产生”Am J Respir Crit Care Med。

諏訪部 章: "肺の生体防御-肺サーファクタントと肺胞II型細胞の役割"日本界面医学会雑誌. 30. 1-12 (1999)

Akira Suwabe：“肺的生物防御 - 肺表面活性剂和肺泡 II 型细胞的作用”日本表面医学会杂志 30. 1-12 (1999)。

諏訪部 章: "呼吸器関連の細胞株培養と応用・第1回肺胞上皮細胞(方法論)"分子呼吸器病. 3(1). 46-48 (1999)

Akira Suwabe：“呼吸相关细胞系培养和应用 - 第一肺泡上皮细胞（方法）”《分子呼吸疾病》3(1)。

諏訪部章: "肺の生体防御―肺サーファクタントと肺胞II型細胞の役割"日本界面医学会雑誌. 30. 1-12 (1999)

Akira Suwabe：“肺生物防御 - 肺表面活性剂和肺泡 II 型细胞的作用”日本表面医学会杂志 30. 1-12 (1999)。

Akira Suwabe: "Effects of artificical surfactant on the experimental lung injury. - Studies on lung fibrosis and various lung cells -"Clinical Pulmonary Phisiology. 30(2). 11-15 (1998)

Akira Suwabe：“人造表面活性剂对实验性肺损伤的影响。-肺纤维化和各种肺细胞的研究-”临床肺生理学。