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CELLULAR INVESTIGATION AND ANALYSIS OF INDUCTION MECHANISMS OF IN VITRO LANGHANS TYPE-MULTINUCLEATED GIANT CELL FORMATION

Research Project

Project/Area Number 11670855
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionKANSAI MEDICAL UNIVERSITY

Principal Investigator

OKAMOTO Hiroyuki  KANSAI MEDICAL UNIVERSITY / DEPARTMENT OF DERMATOLOGY ASSOCIATE PROFESSOR, 医学部, 助教授 (10142291)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsGranuloma / Sarcoidosis / Multinucleated Giant Cells / MDP / Langhans-type / Foreign body-type / CD14 / CD16 / Tranilast / 単球
Research Abstract

The supernatant of concanavalin A-stimulated human peripheral blood mononuclear cells (conditioned medium) generated multinucleated giant cells (MGC) ; Langhans type-(LGC) and foreign body type-MGC (FGC). MDP (N-acetylmuramyl-L-alanyl-D-isoglutamine), a structural analogue of part of the bacterial peptidoglycan, augmented the frequency of LGC.Adhesion molecules and cytokines such as IFN-γ, GM-CSF and IL-3 were found to play an important role in MGC formation but not in LGC induction. Extracellular matrix was also important for MGC formation, particularly cellular fibronectin for LGC induction. MGC were produced by conditioned medium from CD 14^<++> CD 16 monocytes but not from CD 14^+CD16^+ monocytes or immature dendritic cells induced by GM-CSF and IL-4, and slightly from macrophages induced by M-CSF.Addition of MDP did not generate MGC from CD14^+CD16^+ monocytes or dendritic cells but slightly enhanced LGC formation from macrophages. Fusion index of LGC from CD 14^<++> CD16^+ monocytes were enhanced by MDP as same as that in whole monocytes. Next, we examined MGC formation from monocytes of patients with sarcoidosis. MGC were more highly produced from monocytes of sarcoidosis patients than healthy control subjects. The susceptibility of monocytes cultured in conditioned medium for 24 hrs to Bz-ATP-mediated cytolysis was significantly higher in sarcoidosis patients than normal subjects, suggesting that the ability of monocytes to produce MGC through purinergic receptors was enhanced in sarcoidosis patients. Finally, we examined the in vitro effect of tranilast on the formation of MGC.Tranilast inhibited the formation of both types of MGC dose-dependently. Immuno-histochemical stainings showed that tranilast-treated monocytes had less expression of ICAM-1. These findings suggest that tranilast has an efficacy for cutaneous lesions in some cases of granulomatous disorders partly through a direct effect on monocyte/macrophage-lineage cells.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Okamoto.H: "Evaluation of apoptotic ceus induced by ultraviolet light B radiation in epidermal sheets stained by the TUNEL technique"J.Invest.Dermatology. 113. 802-807 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okamoto.H: "Epidermal changes in cutaneous lesions of sarcoisosis"American J Dermatology. 21. 229-233 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okamoto.H: "Cutaneous sarcoidosis with cardiac involvement"European J Dermatology. 9. 466-469 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morita K: "Papular electrolytic giant cell granuloma : a clinical variant of annular electrolytic giant ceu granuloma or generalized granuloma annular?"European J Dermatology. 9. 647-649 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujii K.: "Recurrent follicular and lichenoid papules of sarcoidosis"European J Dermatology. 10. 303-305 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizuno K.: "Inhibitory influences of trainlast on multiruscleated giant cereformation from monocytes by supernatant of car A-stimulated mononuclear cells"J Drmatological Science. 24. 166-170 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kobayashi K, Imai T, Adachi S, Yoifuji T, Furusho K, Kore-eda S, Mizuno K, Okamoto H: "Juvenile xanthogranuloma with hematologic changes in dizygotic twins : report of two newborn infants"Pediatric Dermatology. 15. 203-206 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okamoto H, Mizuno K, Ohkuwa T: "Unilateral linear lichen sclerosus et atrophicus"European Journal of Dermatology. 8. 575-577 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohkura T, Mizuno K, Yoshikawa Y, Ohta K, Okamoto H, Imamura S: "A case of sarcoidosis with polymorphic eruptions on generalized skin areas."Rinsho Derma (Japanese). 40. 2071-2073 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okamoto H: "Epidermal changes in cutaneous lesions of sarcoidosis."American Journal of Dermatopathology. 21. 229-233 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okamoto H, Mizuno K, Ohtoshi E: "Cutaneous Sarcoidosis with Cardiac Involvement."European Journal of Dermatology. 9. 466-469 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okamoto H, Mizuno K, Itoh T, Tanaka K, Horio T: "Evaluation of Apoptotic Cells Induced by Ultraviolet Light B Radiation in Epidermal Sheets Stained by the TUNEL Technique."Journal of Investigative Dermatology. 113. 802-807 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morita K, Okamoto H, Miyachi Y: "Papular elastolytic giant cell granuloma : a clinical variant of annular elastolytic giant cell granuloma or generalized granuloma annulare?"Eur J Dermatol. 9. 647-649 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsumura, K.Mizuno, K.Ohta, H.Okamoto, S.Imamura: "A case of cutaneous polyarteritis nodosa associated with ulcerative colitis."Brit J Dermatol. 142. 560-562 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujii K, Okamoto H, Onuki M, Horio T: "Recurrent follicular and lichenoid papules of sarcoidosis"Eur J Dermatol. 10. 303-305 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizuno K, Okamoto H, Horio T: "Inhibitory influences of tranilast on multinucleated giant cell formation from monocytes by supernatant of conA-stimulated mononuclear cells."J Dermatol Science. 24. 166-170 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kana Mizuno et al: "Inhibitory influences of tranilast on multinucleated giant cell formation from monocytes by supernatant of concanavalin A-stimulated mononuclear cells"J.Dermatological Science. 24(2). 166-170 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Keiko Fujii et al: "Recurrent follicular and lichenoid papules of sarcoidosis"European J Dermatology. 10(4). 303-305 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kazumasa Morita et al: "Papular elastolytic giant cell granuloma : a clinical variant of annular elastolytic giant cell granuloma or generalized granuloma annulare"European J Dermatology. 9(8). 647-649 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] 岡本祐之: "非感染性肉芽腫性な有疾患の臨床像と組織学的特徴"日本サルコイドーシス学会誌. 20(1). 15-20 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hiroyuki Okamoto: "Epidermal changes in cutaneous lesions of sarcoidosis"American Journal of Dermatopathology. 21. 229-233 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroyuki Okamoto: "Cutaneous sarcoidosis with cardiac involvement"European Journal of Dermatology. 9. 466-469 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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