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2001 Fiscal Year Final Research Report Summary

Evaluations of Specific Endothelial Cell Markers in Lung Alveolar Capillaries

Research Project

Project/Area Number 11470143
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNippon Medical School

Principal Investigator

KAWANAMI Oichi  Nippon Medical School, Institute of Gerontology, Professor, 老人病研究所, 教授 (70096973)

Co-Investigator(Kenkyū-buntansha) FUJIWARA Masakazu  Nippon Medical School, Institute of Gerontology, Lecturer, 老人病研究所, 助手 (20312069)
JIN Enjing  Nippon Medical School, Institute of Gerontology, Lecturer, 老人病研究所, 助手 (10312068)
GHAZIZADEH Mohammad  Nippon Medical School, Institute of Gerontology, Associate Professor, 老人病研究所, 助教授 (30190979)
EMI Mitsuru  Nippon Medical School, Institute of Gerontology, Professor, 老人病研究所, 教授 (90221118)
OHTA Shigeo  Nippon Medical School, Institute of Gerontology, Professor, 老人病研究所, 教授 (00125832)
Project Period (FY) 1999 – 2001
Keywordsalveolar capillary / vascular endothelial cell / protease-activated receptor / thrombomodulin / thrombin / lung adenocarcinoma / lung injury / serine protease
Research Abstract

Morphology of the alveolar capillaries in the lung has been well documented under healthy and pathologic conditions. However, so-far available results could be summarized as plain observations by light and electron microscopies, and the functional implication derived from them is far from satisfactory. In order to explain and evaluate phenotypic activation of alveolar capillary endothelial cells, our observation has been focusing on a single unit capillary of alveolar walls in the lung. Together with electron and confocal laser scanning microscopies, multiple probing antigens, including anticoagulant thrombomodulin (TM), coagulant von Willebrand factor (vWf), protease-activated receptors (PAR) and their ligand-serine proteases, have been applied on human and experimental animal lungs. Important and novel findings we have obtained were as follows : 1) alveolar capillary endothelium lacked a conventional expression of vWf, but fully covered by TM ; 2) immunohistochemical conversion, from TM- to vWf-dominant phenotype, underwent when alveolar walls were damaged or metastasized by neoplastic cells of primary lung adenocarcinoma ; 3) PAR in endothelial cells elicited by nearby neoplastic cells facilitated a loss of TM while vWf started to accumulate ; and 4) activation of PAR on endothelial cells by serine proteases such as thrombin lead to exert a variety of biological activities, including cell growth and collagen production in alveolar wall cells. Thus, alveolar capillary endothelial cells might at least partly be a primary stimulator for repairing alveolar damages. In this connection alveolar capillary endothelial cells would be deeply involved in promoting cellular network functions among the alveolar wall cells. Our research aims are forwarding further to evaluate basic functions of endothelial cells in collagen vascular disease-related lung fibrosis.

  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Liu A M, Ghazizadeh M, Onouchi Z, Asano G.: "Ultrastructutral characteristics of myocardial and coronary microvascular lesions in Kawasaki disease"Microvasc.Res.. 58・. 10-27 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 川並汪一, 金恩京: "間質性肺炎と肺微小血管内皮細胞:障害と修復に対する領域別の特性"Molecular Medicine. 36・. 74-85 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 榎本達治, 川並汪一, 工藤翔二, 佐藤雅史, 中田紘一郎, 他: "ランゲルハンス細胞性肉芽腫症の気管支肺胞洗浄液中に出現する特異な組織球"呼吸. 18・. 528-536 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawanami O, Jin E, Ghazizadeh M, Fujiwara M, Jiang L, et al.: "Mosaic-like distribution of endothelial cell antigens in capillaries and juxtaalveolar microvessels in the normal human lung"Pathol.Int.. 50・2. 136-141 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawanami O, Jin E, Ghazizadeh M, Fujiwara M, Jiang L, et al.: "Heteregeneous distribution of thrombomodulin and von Willebrand factor in endothelial cells in the human pulmonary microvessels"J.Nippon Med.Sch.. 67・2. 118-125 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Jin E, Kawanami O.: "Unique distribution of von Willebrand factor and thrombomodulin in endothelial cells of human pulmonary microvessels"J.Nippon Med.Sch.. 67・2. 64-65 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Jin E, Ghazizadeh M, Fujiwara M, I Nagashima M, Kawanami O, et al.: "Angiogenesis and phenotypic alteration of alveolar capillary endothelium in areas of neoplastic cell spread in primary lung adenocarcinoma"Pathol.Int.. 51・9. 691-700 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi T, Azuma A, Abe S, Kawanami O, Ohara K, Kudoh: "Significance of lymphocytosis in bronchoalveolar lavage in suspected ocular sarcoidosis"Eur.Respir.J.. 18・3. 515-521 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Jin E, Fujiwara M, Nagashima M, Shimizu H, Kawanami O, et al.: "Aerogenous spread of primary lung adenocarcinoma induces ultrastructural remodeling of the alveolar capillary endothelium"Hum.Pathol.. 32・10. 1050-1058 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamano G, Funahashi H, Kawanami O, Zhao LX, Ban N, Uchida Y, et al.: "ABCA3 is a lamellar body membrane protein in human lung alveolar typeII cells(1)"FEBS Lett.. 16・508. 221-225 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Obara K, Ghazizadeh M, Shimizu H, Arai R, Tenjin T, Kawanami O, et al.: "Comprative genomic hybridization study of genetic changes associated with vindesine resistance in esophageal carcinoma"Int.J.Oncology.20(2):255-260.2002 Feb.. 20・2. 255-260 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujiwara M, Jin E, Ghazizadeh M, Kawanami O: "Antisense oligodeoxynucleotides against thrombomodulin suppress the cell growth of lung adenocarcinoma cell line A549 cells"Pathol.Int.52:204-213.2002 Apr.. 52・20. 204-213 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shen G H, Ghazizadeh M, Kawanami O, Kurihara Y, Ghazizadeh M, et al.: "Propostic significance of vascular endothelial growth factor expression in human ovarian carcinoma"Brit.J.Cancer 83(2):196-2O3.2000 July.. 83・2. 196-203 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arai, R, Ghazizadeh M, Kawanami O: "Comparative genomic hybridization analysis of cisplatin-resistant ovarian carcinoma cells"J.Nippon Med.Sch.. 67・. 416-417 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujiwara M, Jin E, Ghazizadeh M, Kawanami O.: "An in vitro model to evaluate regulatory mechanisms of antigen expression by normal pulmonary vessel endothelial cells"Microvasc.Res.. 61・2. 215-219 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imai J, Ghazizadeh M, Naito Z, Asano G.: "Immunohistochemical expression of T, Tn and sialyl-Tn antigens and clinical outcome in human breast carcinoma"Anticancer Res.. 21・2B. 1327-1334 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ozaki N, Ishizaki M, Ghazizadeh M, Yamanaka N.: "Apoptosis mediates decrease in cellularity during the regression of Arthus reaction in cornea"Br.J.Ophthalmol.. 85・5. 613-618 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshimura C, Miyamasu M, Nagase H, Iikura M, Kawanami O, et al.: "Morita Y, Iwata T, Yamamoto K, Hirai K.: Glucocorticoids induce basophil apoptosis"J.Allergy Clin.Immunol.. 108・2. 215-220 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurihara Y, Ghazizadeh M, Bo H, Shimizu H, Kawanami O, et al.: "Genome-wide screening of laser capture microdissected gastric signet-ring cell carcinomas"J.Nippon Med.Sch.. (In press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Jin E, Fujiwara M, Ghazizadeh M, Takemura T, Kawanami O: "Protease-activated receptors participate alveolar capillary angiogenesis in lung adenocarcinoma"(submitted). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Liu A M, Ghazizadeh M, Onouchi Z, Asano G.: "Ultrastructural characteristics of myocardial and coronary microvascular lesions in Kawasaki disease"Microvasc. Res.. 58. 10-27 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawanami O, Jin E, Ghazizadeh M, Fujiwara M, Jiang L, Ohaki Y, Gomibuchi M, Takemura T.: "Mosaic-like distribution of endothelial cell antigens in capillaries and juxtaalveolar microvessels in the normal human lung"Pathol. Int.. 50(2). 136-141 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawanami O, Jin E, Ghazizadeh M, Fujiwara M, Jiang L, Takemura T, Ohaki Y, Gomibuchi M, Arai S, Takeda K, Yu ZX, Ferrans V J.: "Heteregeneous distribution of thrombomodulin and von Willebrand factor in endothelial cells in the human pulmonary microvessels"J. Nippon Med.Sch.. 67(2). 118-125 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jin E, Kawanami O.: "Unique distribution of von Willebrand factor and thrombomodulin in endothelial cells of human pulmonary microvessels"J. Nippon Med.Sch.. 67(2). 64-65 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shen G H, Ghazizadeh M, Kawanami O, Shimizu H, Jin E, Araki T, Sugisaki Y.: "Prognostic significance of vascular endothelial growth factor expression in human ovarian carcinoma"Brit. J. Cancer. 83(2). 196-203 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Arai, R, Ghazizadeh, M, Kawanami O.: "Comparative genomic hybridization analysis of cisplatin- resistant ovarian carcinoma cells"J. Nippon Med.Sch.. 67. 416-417 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujiwara M, Jin E, Ghazizadeh M, Kawanami O.: "An in vitro model to evaluate regulatory mechanisms of antigen expression by normal pulmonary vessel endothelial cells"Microvasc. Res.. 61(2). 215-219 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Imai J, Ghazizadeh M, Naito Z, Asano G.: "Immunohistochemical expression of T, Tn and sialyl-Tn antigens and clinical outcome in human breast carcinoma"Anticancer Res.. 21(2B). 1327-1334 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ozaki N, Ishizaki M, Ghazizadeh M, Yamanaka N.: "Apoptosis mediates decrease in cellularity during the regression of Arthus reaction in cornea"Br. J. Ophthalmol.. 85(5). 613-618 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshimura C, Miyamasu M, Nagase H, Iikura M, Yamaguchi M, Kawanami O, Morita Y, Iwata T, Yamamoto K, Hirai K.: "Glucocorticoids induce basophil apoptosis"J. Allergy Clin. Immunol.. 108(2). 215-220 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jin E, Ghazizadeh M, Fujiwara M, Nagashima M, Shimizu H, Ohaki Y, Arai S, Gomibuchi M, Takemura T, Kawanami O.: "Angiogenesis and phenotypic alteration of alveolar capillary endothelium in areas of neoplastic cell spread in primary lung adenocarcinoma"Pathol. Int.. 15(9). 691-700 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi T, Azuma A, Abe S, Kawanami O, Ohara K, Kudoh.: "Significance of lymphocytosis in bronchoalveolar lavage in suspected ocular sarcoidosis"Eur. Respir. J.. 18(3). 515-521 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jin E, Fujiwara M, Nagashima M, Shimizu H, Ghazizadeh M, Pan X, Arai S, Ohaki Y, Gomibuchi M, Takemura T, Kawanami O.: "Aerogenous spread of primary lung adenocarcinoma induces ultrastructural remodeling of the alveolar capillary endothelium"Hum. Pathol.. 32(10). 1050-1058 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamano G, Funahashi H, Kawanami O, Zhao LX, Ban N, Uchida Y, Morohoshi T, Ogawa J, Shioda S, Inagaki N.: "ABCA3 is a lamellar body membrane protein in human lung alveolar type II cells(1)"FEBS Lett.. 16 ; 508(2). 221-5 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Obara K, Ghazizadeh M, Shimizu H, Arai R, Tenjin T, Suzuki S, Moriyama Y, Kawanami O.: "Comparative genomic hybridization study of genetic changes associated with vindesine resistance in esophageal carcinoma"Int. J. Oncology. 20(2). 255-260 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujiwara M, Jin E, Ghazizadeh M, Kawanami O.: "Antisense oligodeoxynucleotides against thrombomodulin suppress the cell growth of lung adenocarcinoma cell line A549 cells"Pathol. Int.. 52. 204-213 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurihara Y, Ghazizadeh M, Bo H, Shimizu H, Kawanami O, Moriyama Y, Onda M.: "Genome-wide screening of laser capture microdissected gastric signet-ring cell carcinomas"J. Nippon Med. Sch.. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jin E, Fujiwara M, Ghazizadeh M, Takemura T, Kawanami O.: "Protease-activated receptors participate alveolar capillary angiogenesis in lung adenocarcinoma"(submitted). (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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