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Pathobiology of leukocyte functions from cattle with leukocyte adhesion deficiency(BLAD)and trials of bone marrow transplantation to BLAD-cattle.

Research Project

Project/Area Number 09660344
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied veterinary science
Research InstitutionRAKUNO GAKUEN UNIVERSITY,FACULTY OF VETERINARY MEDICINE

Principal Investigator

NAGAHATA Hajime  RAKUNO GAKUEN UNIVERSITY,SCHOOL OF VETERINARY MEDICINE,PROFESSOR, 獣医学部, 教授 (10133571)

Co-Investigator(Kenkyū-buntansha) KUWABARA Mikinori  GRADUATE SCHOOL OF VETERINARY MEDICINE,HOKKAIDO UNIVERSITY,PROFESSOR, 大学院・獣医学研究科, 教授 (10002081)
INANAMI Osamu  GRADUATE SCHOOL OF VETERINARY MEDICINE,HOKKAIDO UNIVERSITY,ASSOC.PROFESSOR, 大学院・獣医学研究, 助教授 (10193559)
TERAOKA Hiroki  RAKUNO GAKUEN UNIVERSITY,FACULTY OF VETERINARY MEDICINE,ASSIST.PROFESSOR, 獣医学部, 講師 (50222146)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsBLAD TRANSFUSION / BONE MARROW TRANSPLANTATION / CD18 / GENETIC DISEASE / TRANSFUSION / CATTLE DISEASE
Research Abstract

The above-entitled study was performed and the results were summarized as follows :
Fc receptor for immunoglobulin G-mediated phagocytosis, superoxide production and intracellular calcium ([Ca^2+]^i) signaling of complement receptor type 3-(CR3) deficient neutrophils from a heifer with leukocyte adhesion deficiency were compared to those of control heifers. The mean phagocytic activity of IgG-coated yeasts and aggregated bovine IgG (Agg-IgG)-induced superoxide production of CR3-deficient neutrophils were 10% and 77.9%, respectively, of those of control neutrophils. The [Ca^2+]^i signals in CR3-deficient neutrophils stimulated with Agg-Igg or concanavalin A were deficient with mean peak [Ca^2+]^i concentrations of 78% and 42% of those of controls. These findings suggest that Fc receptor-mediated neutrophil functions are closely dependent on the presence of CR3 on the neutrophil cell surfaces.
The emigration of leukocytes from calves with B2 integrin deficiency (BLAD) into bronchoalveolar … More spaces and scraped tissues was compared to that of normal calves. Neutrophils were found in bronchoalveolar lavage fluid from BLAD-affected calves showing chronic -pneumonia. The neutrophils were CR3-negative when characterized by flow cytometric analysis using anti-CD18 monoclonal antibody. Chemiluminescent response mediated by CR3 in neutrophils isolated from bronchoalveolar lavage fluid from BLAD-calves showed similar findings obtained from CR3-deficient neutrophils. Neutrophils from normal calves migrated to the scraped tissue, evaluated by skin window method. These findings confirmed the extravasating property of normal and CR3-deficient neutrophils into scraped tissues.
Granulocyte transfusion as performed in an 8-month-old heifer with BLAD to monitor the changes in transfused CDl8-positive neutrophils and associated neutrophil chemilurninescent response in B2 integrin deficient host. The CD18-positive neutrophils were detected in blood from the BLAD heifer during the first 3 hr after 2.6xl0^9cells were infused by GT, and disappeared by 5 hr after GT.The CL response of neutrophils was increased 1.7 to 2.8-fold in the BLAD heifer during the first 3 hr after GT, thereafter CL response decreased gradually from 2 to 5 hr after GT.
Bone marrow transplantation (BMT) was performed in a 9-month-old heifer with BLAD.Clinical and hematological findings, selected neutrophil function and CD18 expression of neutrophils in a B2 integrin-deficient heifer were examined. Twelve months after BMT, a small fluorescent region in the CD18-positive area of a flow cytometric profile was demonstrated and estimated to represent 0.3-0.5% of the CD18-positive neutrophils as measured by flow cytometric analysis following irnmunomagnetic separation. The animal's clinical condition appeared to improve and stabilize over our observation period of 28 months following BMT.Newly expressed CD18 seemed to play an important role in ameliorating the clinical signs of BLAD in this heifer. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Nagahata, H.et al.: "Fcreceptor-mediated phagocytosis, superoxide production and calcium signaling of B_2 integrin-deficient neutrophils." Microbiol.lmmunol.41(9). 747-750 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagahata, H.et al.: "Leukocyte emigration in normal colves and calves with leukocyte adhesion deficiency." J.Vet.Med.Sci.59(12). 1143-1147 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 桑原幹典他: "白血球粘着蛋白質欠損症ホルスタイン牛好中球を用いた活性酸素生成細胞内情報伝達機構の研究" 磁気共鳴と医学. 8. 109-113 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagahata, H.et al.: "Survival of transfused CD18-positire granulocytes and their CL response in a BLAD heifer." J.Vet.Med.Sci.60(2). 261-262 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagahata, H.et al.: "Bone marrow-transplantation in a Holstein heifer with borine leukocyte adhesion deficiency." Vet.J.(Brit.Vet.J.). 156. 15-21 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 永幡 肇: "わが国におけるウシ白血球粘着不全症(BLAD)の輪郭" 獣医畜産新報. 51(11). 939-945 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 永幡 肇: "21世紀の新技術・ブラッドはヒト・ラッドの骨髄移植遺伝子治療のモデル" 酪農学園大学エクステンションセンター(分担執筆), 119-129p (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Nagahata: "Fc receptor-mediated phagocytosis, superoxide production and calcium signaling of B2 integrin-deficient bovine neutrophils." Microbol.Immunol.41. 747-750 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Higuchi: "Relationship between the chemiluminescent response of bovine neutrophils and changes in intracellular free calciumconcentration" Can.J.Vet.Res.61. 57-61 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Nagahata: "Leukocyte emigration in normal calves and calves with leukocyte adhesion deficiency." J.Vet.Med.Sci.59. 1143-1147 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Nagahata: "Survival of transfused CD18-positive granulocytes and their chemiluminescent response in a Heifer with leukocyte adhesion deficiency." J.Vet.Med.Sci.60. 261-262 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Nagahata: "Bone marrow transplantation in a Holstein heifer with bovine leukcocyte adhesion deficiency." Vet.J.(Brit.Vet.J.). 156. 15-21 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagahata,H.,et al.: "Survival of transfused CD18-positive granulocytes and their CL response in a BLAD neifer." J.vet.Med.Sci.60(2). 261-262 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nagahata,H.,et al.: "Bone marrow transplantation in a Holstain neifer with bovine leucooyte adhesion deficiency." Vet.(Brit.)J.156. 15-21 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nagahata,H.,et al.: "Analysis of L-selectin and β_2 integrin on normal and CD18-deficient bovine neutrophils." Vet.Pathol.35(5). 439 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 永幡 肇: "わが国におけるウシ白血球粘着不全症(BLAD)の輪郭" 獣医畜産新報. 51(11). 939-945 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nagahata,H.,et al.: "Prevalence and allele frequency estimation of bovine leukocyte adhesion deficiency(BLAD)in Holstein-Friesian cattie in Japan." J.vet.Med.Sci.59(4). 233-238 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nagahata,H.,et al.: "Fc receptor-mediated phagocytosis, superoxide production and calcium signaling of B2 integrin-deficient bovine neutrophils" Microbiol.lmmunol.41(9). 747-750 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nagahata,H.,et al.: "Leukocyte emigration in normal calves and calves with leukocyte adhesion deficiency." J.Vet.Med.Sci.59(12). 1143-1147 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Higuchi,H.,et al.: "Relationship between the chemiluminescent response of borine neutrophils and chauges in 〔Ca^<2+>〕^i concentration." Can.J.Vet.Res.61(1). 57-61 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 桑原幹典他: "白血球粘着蛋白質欠損症ホルスタイン牛好中球を用いた活性酸素生成細胞内情報伝達機構の研究" 磁気共鳴と医学. 8. 109-113 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 永幡肇: "21世紀の新技術・ブラッドはヒト・ラッドの骨髄移植・遺伝子治療のモデル" 酪農学園大学エクステンションセンター(出版部), 119-129 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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