1996 Fiscal Year Annual Research Report

HTLV-I関連脊髄症(HAM)発症病理におけるモノサイト/マクロファージの役割

Research Project

Project/Area Number	08670716
Research Institution	Nagasaki University
Principal Investigator	中村龍文長崎大学, 医学部附属病院, 講師 (00198219)
Co-Investigator(Kenkyū-buntansha)	調漸長崎大学, 医学部附属病院, 助手 (40264220)
Keywords	HTLV-I関連脊髄症 / モノサイト / マクロファージ / HTLV-I / 遺伝子導入 / iNOS / NO
Research Abstract	HTLV-I関連脊髄症(HAM)患者及び対照疾患(OND)患者末梢血より,Nicodenz法を用いて単離したmonocyte/macrophage(Mo/Mφ)を培養し,培養上清中の炎症性サイトカインとnitric oxide(NO)濃度を測定した.その結果,HAM患者末梢血Mo/MφはLPS非刺激時と比較し,LPS刺激下の培養上清中TNF-α,NO濃度は有意に上昇した.特にLPS刺激下培養上清中NO濃度は,HAM患者末梢血Mo/MφがOND末梢血Mo/Mφと比較し有意に高値であった.このことからHAM患者末梢血MO/Mφは易活性化状態にあると考えられ,サイトカインやNOを介したHAM発症への関与が推定された. 次に,ヒト・マクロファージ細胞株U937にサイトメガロウィルスをプロモーターとしたtax発現プラスミドをリポフェクション法にて遺伝子導入し,inducible mitric oxide synthase(iNOS) mRNA発現能及びNO産生能を検討した.iNOSmRNA発現量はtaxを遺伝子導入したU937で高値を示し,IFN-γ刺激により更に誘導された.培養上清中のNO濃度はIFN-γ非刺激に於いてもtaxを遺伝子導入したU937で高く,IFN-γ刺激により更に増強された.以上より,マクロファージ系細胞はHTLV-I感染でNO産生能が修飾され,神経細胞障害を獲得する事が示唆された. Yoshikiらによって作成されたHAMモデルラットの組織所見がマクロファージ/ミクログリアを中心とした神経変性像が主体であることや,KurodaらがHAM患者剖検脊髄のマクロファージ/ミクログリア系細胞内にHTLV-I privoral genomeの存在を示唆したこれまでの知見と併せて,我々のこれまでの研究結果は,HAM発症にMo/Mφが関与していることを示していると考えられる.

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] Tatsufumi Nakamura,et al.: "Spontaneous proiferation of and cytokine production by T cells adherent to human endothelial cells in patients with human T-Iymphotropic virus type I-associated myelopathy." Internal Med. 35. 195-199 (1996)
[Publications] Jun Suzuki,et al.: "The association of antibodies against human T cell Iymphotroprc virus type I (HILV-I) pX gene mutant products with HTLV-I-associated myelopathy/tropical spastic paraparesis." J Infect Dis. 173. 1115-1122 (1996)
[Publications] Kiyosumi Ohishi,et al.: "Autoantibodies and immunoglobulins in atomic bomb survivors with human T-Iymphitropic virus type I." Internal Med. 35. 624-628 (1996)
[Publications] Yoshihiro Nishiura,et al.: "Increased production of inflammatory cytodines in cultured CD4+ cells from patients with HTLV-I-associated myelopathy." Tohoku J Exp Med. 179. 227-233 (1996)
[Publications] Katsuhiro Ichinose,et al.: "Characterization of T cells transmigrating through human endothelial cells in patients with HTLV-I associated myelopathy." Immunobiol. 196. 485-490 (1996)
[Publications] Akira Tsujino,et al.: "Pentoxifylline down-regulates adhesion molecule expression and inflammatory cytokine production in cultured peripheral blood mononuclear cells from patients with HTLV-I-associated" J Neuroimmunol. (in press). (1997)
[Publications] Hideki Nakamura,et al.: "High prevalence of Sjoren's syndrome in patients with HTLV-I-associated myelopathy." Ann Rheumatic Dis. (in press). (1997)
[Publications] Takafumi Furuya,et al.: "Heightend transmigrating activity of CD4-positive T cells through reconstituted basement membrane in patients with human T lymphotropic virus type I-assicoated myelopathy." Proceedings of the Association of American Physicians. (in press). (1997)
[Publications] Susumu Shirabe,et al.: "A successful application of pentoxifylline in treatment of HTLV-I associated Myelopathy." J Neurol Sci. (in press). (1997)
[Publications] 中村龍文: "HAM患者T細胞の血管内皮細胞への接着と基底膜透過能" 神経免疫学. 4. 22-24 (1996)
[Publications] 中村龍文,他: "HAMと細胞間接着因子" 現代医療. 28. 2265-2269 (1996)
[Publications] 中村龍文,他: "HAM" 内科. 77. 1396-1397 (1996)
[Publications] 江口勝美,他: "HTLV-I感染とシェ-グレン症候群" 免疫・Immunology Frontier. 7. 35-39 (1997)

1996 Fiscal Year Annual Research Report

HTLV-I関連脊髄症(HAM)発症病理におけるモノサイト/マクロファージの役割

Principal Investigator

中村 龍文 長崎大学, 医学部附属病院, 講師 (00198219)

Research Products

[Publications] Tatsufumi Nakamura,et al.: "Spontaneous proiferation of and cytokine production by T cells adherent to human endothelial cells in patients with human T-Iymphotropic virus type I-associated myelopathy." Internal Med. 35. 195-199 (1996)

[Publications] Jun Suzuki,et al.: "The association of antibodies against human T cell Iymphotroprc virus type I (HILV-I) pX gene mutant products with HTLV-I-associated myelopathy/tropical spastic paraparesis." J Infect Dis. 173. 1115-1122 (1996)

[Publications] Kiyosumi Ohishi,et al.: "Autoantibodies and immunoglobulins in atomic bomb survivors with human T-Iymphitropic virus type I." Internal Med. 35. 624-628 (1996)

[Publications] Yoshihiro Nishiura,et al.: "Increased production of inflammatory cytodines in cultured CD4+ cells from patients with HTLV-I-associated myelopathy." Tohoku J Exp Med. 179. 227-233 (1996)

[Publications] Katsuhiro Ichinose,et al.: "Characterization of T cells transmigrating through human endothelial cells in patients with HTLV-I associated myelopathy." Immunobiol. 196. 485-490 (1996)

[Publications] Akira Tsujino,et al.: "Pentoxifylline down-regulates adhesion molecule expression and inflammatory cytokine production in cultured peripheral blood mononuclear cells from patients with HTLV-I-associated" J Neuroimmunol. (in press). (1997)

[Publications] Hideki Nakamura,et al.: "High prevalence of Sjoren's syndrome in patients with HTLV-I-associated myelopathy." Ann Rheumatic Dis. (in press). (1997)

[Publications] Takafumi Furuya,et al.: "Heightend transmigrating activity of CD4-positive T cells through reconstituted basement membrane in patients with human T lymphotropic virus type I-assicoated myelopathy." Proceedings of the Association of American Physicians. (in press). (1997)

[Publications] Susumu Shirabe,et al.: "A successful application of pentoxifylline in treatment of HTLV-I associated Myelopathy." J Neurol Sci. (in press). (1997)

[Publications] 中村龍文: "HAM患者T細胞の血管内皮細胞への接着と基底膜透過能" 神経免疫学. 4. 22-24 (1996)

[Publications] 中村龍文,他: "HAMと細胞間接着因子" 現代医療. 28. 2265-2269 (1996)

[Publications] 中村龍文,他: "HAM" 内科. 77. 1396-1397 (1996)

[Publications] 江口勝美,他: "HTLV-I感染とシェ-グレン症候群" 免疫・Immunology Frontier. 7. 35-39 (1997)

中村龍文長崎大学, 医学部附属病院, 講師 (00198219)