An importance on bone marrow-derived cells on lung repair

骨髓来源细胞对肺修复的重要性

• 批准号: 13670589
• 负责人: KUBO Hiroshi
• 金额: $ 2.3万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670589/
• 关键词: bone marrow; inflammation; regeneration; LPS; repair; progenitor cell; lung; stem cell; 肺炎; 肺傷害; 骨髄幹細胞; 再生医学; 好中

Tissue repair often occurs in organs damaged by an inflammatory response. Inflammatory stimuli induce a rapid and massive release of inflammatory cells including neutrophils from the bone marrow. Recently, many studies suggested that bone marrow cells have the potential to differentiate into a variety of cell types. However, whether inflammatory stimuli induce release of bone marrow-derived progenitor cells (BMPCs), or how much impact the suppression of BMPCs has on the injured organ is not clear. Here we show that LPS, a component of gram-negative bacterial cell walls, in the lung airways, induces a rapid mobilization of BMPCs into the circulation in mice. BMPCs accumulate within the inflammatory site and differentiate to become endothelial and epithelial cells. Moreover, the suppression of BMPCs by sublethal irradiation prior to intra-pulmonary LPS leads to disruption of tissue structure and emphysema-like changes. Reconstitution of the bone marrow prevents these changes. These data suggest that BMPCs are important and required for lung repair after LPS-induced lung injury.

组织修复通常发生在由炎症反应损伤的器官中。炎性刺激诱导包括中性粒细胞在内的炎性细胞从骨髓中快速大量释放。近年来，许多研究表明骨髓细胞具有分化为多种细胞类型的潜能。然而，炎症刺激是否诱导骨髓源性祖细胞（BMPC）的释放，或者BMPC的抑制对受损器官有多大影响尚不清楚。在这里，我们表明，LPS，革兰氏阴性细菌细胞壁的一个组成部分，在肺气道，诱导BMPC进入小鼠循环的快速动员。BMPC在炎症部位内积聚并分化为内皮细胞和上皮细胞。此外，在肺内LPS之前通过亚致死照射抑制BMPC导致组织结构的破坏和肺气肿样变化。骨髓的重建可以防止这些变化。这些数据表明，BMPC是重要的，需要在LPS诱导的肺损伤后的肺修复。

项目成果

Noda M, Suzuki S, Tsubochi H, Sugita M, Maeda S, Kobayashi S, Kubo H, Kondo T: "Single Dexamethasone injection increases alveolar fluid clearance in adult rats."Critical Care Medicine. 31. 1183-1189 (2003)

Noda M、Suzuki S、Tsubochi H、Sugita M、Maeda S、Kobayashi S、Kubo H、Kondo T：“单次地塞米松注射可增加成年大鼠的肺泡液清除率。”重症监护医学。

Suzuki S, Koyama K, Darnel A, Ishibashi H, Kobayashi S, Kubo H, Suzuki T, Sasano H, Krozowski ZS: "Dexamethasone up-regulates 11[[beta]]-Hydroxysteroid dehydrogenase type 2 in BEAS-2B cells."Am.J.Respir.Crit.Care Med.. 167. 1244-1249 (2003)

Suzuki S、Koyama K、Darnel A、Ishibashi H、Kobayashi S、Kubo H、Suzuki T、Sasano H、Krozowski ZS：“地塞米松上调 BEAS-2B 细胞中的 11β]-羟基类固醇脱氢酶 2 型。”

Ishida I, Kubo H, Suzuki S, Suzuki T, Akashi S, Inoue K, Maeda S, Kikuchi H, Sasaki H, Kondo T.: "Hypoxia diminishes Toll-like receptor 4 expression through ROS generated by mitochondria in endothelial cells"J. Immunology. 169. 2069-2075 (2002)

Ishida I、Kubo H、Suzuki S、Suzuki T、Akashi S、Inoue K、Maeda S、Kikuchi H、Sasaki H、Kondo T.：“缺氧通过内皮细胞线粒体产生的 ROS 减少 Toll 样受体 4 的表达”J

Tsubochi H, Suzuki S, Kubo H, Ueno T, Yoshimura T, Suzuki T, Sasano H, Kondo T: "Early Changes in Alveolar Fluid Clearance by Nitric Oxide after Endotoxin Instillation in Rats."Am.J.Respir.Crit.Care Med.. 167. 205-210 (2003)

Tsubochi H、Suzuki S、Kubo H、Ueno T、Yoshimura T、Suzuki T、Sasano H、Kondo T：“大鼠内毒素滴注后一氧化氮对肺泡液清除的早期变化。”Am.J.Respir.Crit.Care

Yamada M, Kubo H, Kobayashi S, Ishizawa K, Numasaki M, Ueda S, Suzuki T, Sasaki H.: "Bone marrow-derived progenitor cells are important for lung repair after LPS-induced lung injury."J.Immunology. 172. 1266-1272 (2004)

Yamada M、Kubo H、Kobayashi S、Ishizawa K、Numasaki M、Ueda S、Suzuki T、Sasaki H.：“骨髓来源的祖细胞对于 LPS 诱导的肺损伤后的肺修复非常重要。”J.Immunology。