An importance on bone marrow-derived cells on lung repair

• Project/Area Number: 13670589
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Tohoku University
• Principal Investigator: KUBO Hiroshi Tohoku University Hospital, Research Associate, 医学部附属病院, 助手 (20332504)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
• Keywords: 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

Research Abstract

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.

Research Products

• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hirai H, Kubo H, Yamaya M, Nakayama K, Numasaki M, Kobayashi S, Suzuki S, Shibahara S, Sasaki H.: "Microsatellite polymorphism in heme oxygenase-1 gene promoter is associated with susceptibility to oxidant-induced apoptosis in lymphoblastoid cell lines."Blood. 102. 1619-1621 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ohrui T, Kubo H, Sasaki H.: "Care for the Older People."Int.Med.. 42. 932-940 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hirai H, Kubo H, Yamaya M, Nakayama K, Numasaki M, Kobayashi S, Suzuki S, Shibahara S, Sasaki H.: "Microsatellite polymorphism in heme oxygenase-1 gene promoter is associated with susceptibility to oxidant-induced apoptosis in lymphoblastoid cell lines"Blood. 102. 1619-1621 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ohrui T, Kubo H, Sasaki H.: "Care for the Older People"Int. Med.. 42. 932-940 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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. 15;169(4). 2069-2075 (2002)
• [Publications] 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)
• [Publications] 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)
• [Publications] 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)