1995 年度実績報告書

IL8抗体のヒト型化とサイトカイン遺伝子調節因子NFkBを標的とした抗炎症剤開発

研究課題

研究課題/領域番号	07557031
研究種目	試験研究(B)
研究機関	金沢大学
研究代表者	松島綱治金沢大学, がん研究所, 教授 (50222427)
研究分担者	山崎達美中外製薬, 探索研究所, 所長向田直史金沢大学, がん研究所, 助教授 (30182067)
キーワード	インターロイキン8 / 抗体 / ヒト型化 / NFkB / 抗炎症剤
研究概要	1)抗IL-8抗体のヒト型化マウス抗ヒトIL-8抗体WS-4を産生するハイブリドーマから、total RNAを抽出し、PCR-cloning法によって、WS-4抗体のH鎖ならびにL鎖をの可変領域をコードするcDNAを単離した。このcDNAをもとに、H鎖についてはその構造が最も類似していたヒト抗体VDR26を鋳型として、L鎖についても構造の類似していたヒト抗体REIを鋳型として、再構成したヒト型化抗体発現ベクターを作成した。これらの両者の発現ベクターを遺伝子導入したCOS細胞培養上清中より、ヒト型化抗体を精製した。精製した抗体は、固相に固定化したヒトIL-8と結合するのみならず、ヒトIL-8のヒト好中球への結合も、元々のモノクローナル抗体と同様に抑制することも証明した。しかし、H鎖の鋳型に用いたVDR26はlgG1に属し、好中球などに存在するFcレセプターとの結合する可能性があることから、現在lgG4に属するヒトigG抗体を鋳型としたヒト型化抗体の作成も試みている。 2)NF-kB活性化に関与する分子を標的とする抗炎症剤の開発ヒト単球性白血病細胞株THP-1の細胞質分画を用い、リポ多糖類(LPS)刺激によって誘導される、lkBaのリン酸化酵素の精製を行い、ほぼ純品に近く精製された。現在、この純品のアミノ酸配列の決定を試みている。一方で、粗精製したlkBaリン酸化酵素を用い、lkBaのリン酸化部位の同定を行い、C末端側の279から303番目のアミノ酸からなる、酸性アミノ酸に富んだ部位であることが判明した。そのなかでも、LPS刺激によって誘導されるリン酸化酵素は主に293Serをリン酸化する以外に、288Ser・291Thrもリン酸化することを明らかにした。しかも、C末端側の279から303番目のアミノ酸に相当するペプチドによって、無細胞系で認められるLPS依存性に起きるNF-kB活性化とIkBaリン酸化が抑制されることを明らかにして、J.Bio.Chem.に報告した。

研究成果

(61件)

すべてその他

すべて文献書誌 (61件)

[文献書誌] Okamoto,S.-i.: "The interleukin-8 AP-1 and kB-like sites are genetic end targets of FK506-sensitive pathway accompanied by calcium mobilization" J. Biol. Chem.269. 8582-8589 (1994)
[文献書誌] Mukaida,N.: "Novel mechanism of glucocorticoid-mediated gene repression: Nuclear factor-kB is target for glucocorticoid-mediated interleukin 8 gene repression" J. Biol. Chem.269. 13289-13295 (1994)
[文献書誌] Nakano,Y: "Protection against lethal bacterial infection in mice by monocyte-chemotactic and -activating factor(MACF)." Infect. Immun.62. 377-383 (1994)
[文献書誌] Murakami,S.: "Transactivation of human hepatitis B virus X protein, HBx, operates through a mechanism distinct from protein kinase C and okadaic acid activation pathway." Virology. 199. 243-246 (1994)
[文献書誌] Asano,T.: "Liposomal muramyl tripeptide up-regulates interleukin-1 alpha, interuleukin-1 beta, tumor necrosis factor-alpha, interleukin-6 and interleukin-8 gene expression in human monocytes." J. Pharmacol. Exp. Ther.268. 1032-1039 (1994)
[文献書誌] Kuno,K.,: "Acid sphingomyelinase is not essential for the IL 1 and tumor necrosis factor receptor signaling pathway leading to NFkB activation." Int. Immunol.6. 1269-1272 (1994)
[文献書誌] Kuno,K.: "The IL 1 receptor signaling pathway" J. Leukocyte Biology. 56. 542-547 (1994)
[文献書誌] Endo,H.: "Experimental arthritis induced by continuous infusion of IL-8 into rabbit knee joints." Clin. Exp. Immunol.96. 31-35 (1994)
[文献書誌] Harada,A.: "Cloning of a cDNA encoding a mouse homolog of the interleukin-8 receptor." Gene. 142. 297-300 (1994)
[文献書誌] Deleuran,B.: "Localisation of interleukin 8 in the synovial membrane, cartilage-pannus junction and chondrocytes in rheumatoid arthritis. Scand." Scand. J. Rheumatol.23. 2-7 (1994)
[文献書誌] Asano,T.: "Liposome-encapsulated muramyl tripeptide up-regulates monocyte chemotactic and activating factor gene expression in human monocytes at the transcriptional and post-transcriptional levels." Cancer Immunology and Immunotherapy. 38. 16-22 (1994)
[文献書誌] Oliveira,I.C.: "Transcriptional inhibition of the interleukin-8 gene by interferon is mediated by the NF-kB site." Mol. Cell Biol.14. 5300-5308 (1994)
[文献書誌] Akahoshi,T.: "Essential involvement of interleukin-8 in neutrophil recruitment in rabbits with acute experimental arthritis induced by lipopolysaccharide and interleukin-1." Lymphokine Cytokine Res.13. 113-116 (1994)
[文献書誌] Itoh,R.: "Interleukin-8 in Behcet's Disease." J. Dermatology. 21. 397-404 (1994)
[文献書誌] Mizuno,K.: "Spontaneous production of interleukin-8 by human lung cancer cells and its augmentation by tumor necrosis factor alpha and interleukin-1 at protein and mRNA levels." Oncology. 51. 467-471 (1994)
[文献書誌] Ito,A.: "Suppression of interleukin 8 production by progesterone in rabbit uterine cervix." Biochem. J.301. 183-186 (1994)
[文献書誌] Kasahara,K.: "Selective expression of monocyte chemotactic and activating factor/monocyte chemoattractant protein 1 in human blood monocytes by mycobacterium tuberculosis." J. Infectious Dis.170. 1238-1247 (1994)
[文献書誌] Murayama,T.: "Elevated cytokine levels in synovial fluid of rheumatoid arthritis correlates with the presence of cytomegalovirus genome." Autoimmunity. 17. 333-337 (1994)
[文献書誌] Wada,T.: "Detection of urinary interleukin-8 in glomerular diseases." Kidney Int.46. 455-460 (1994)
[文献書誌] Nakamoto,Y.: "Detection of the putative E2 protein of hepatitis C virus in human liver." J. Med. Virology. 42. 374-379 (1994)
[文献書誌] Wada,T.: "Appearance of interleukin-8 in the Urine Predicts Acute rejection of Renal Transplantation." Nephrol. Dial. Transplant.9. 874-875 (1994)
[文献書誌] Wada,T.: "Prevention of proteinuria in acute immune complex-mediated glomerulonephritis by an antibody against interleukin 8." J. Exp. Med.180. 1135-1140 (1994)
[文献書誌] Murayama,T.: "Enhancement of human cytomegalovirus replication in human lung fibroblast cell line by interleukin 8." J. Virol.68. 7582-7584 (1994)
[文献書誌] Mukaida,N.: "Molecular mechanism of interleukin 8(IL-8)gene expression." J. Leukocyte Biology. 56. 554-558 (1994)
[文献書誌] Harada,A.: "Essential involvement of interleukin 8(IL 8)in acute inflammation." J. Leukocyte Biology. 56. 559-564 (1994)
[文献書誌] Oishi,K.: "Role of interleukin-8(IL-8)and an inhibitory effect of erythromycin on IL-8 release in the airways of patients with chronic airway diseases." Infect. Immun.62. 4145-4152 (1995)
[文献書誌] Ko,Y.-C.: "Specific elevation of interleukin-8 levels in peritoneal dialysates of patients on continous ambulatory peritoneal dialysis with peritonitis." J. Clin. Pathol.48. 115-119 (1995)
[文献書誌] Morohashi,H.: "Expression of both types of human interleukin 8(IL-8)receptors on mature neurtophils, monocyts, and CD16+lymphocytes." J. Leukocyte Biol.57. 180-187 (1995)
[文献書誌] Yano,S.: "Differential effects of anti-inflammatory cytokines(IL-4,IL-10,and IL-13)on tumorcidal and chemotactic properties of human monocytes induced by monocyte chmotactic and activating factor(MCAF)." J. Leukcyte Biol.57. 303-309 (1995)
[文献書誌] Yasumoto,K.: "Molecular analysis of cytokine network involved in causing cachexia in colon 26 adenocarcinoma-bearing mice." Cancer Res.55. 921-927 (1995)
[文献書誌] Ishikawa,Y.: "Establishment of lipopolysaccharide-dependent nuclear factor-kB activation in a cell-free system." J. Biol. Chem.270. 4158-4164 (1995)
[文献書誌] Watanabe,S.-i.: "Prevention of endotoxin shock by an antibody against leukocyte integrin b2 through inhibiting production and action of tumor necrosis factor." Intl. Immunol.7. 1037-1046 (1995)
[文献書誌] Hoshino,Y.: "Monocyte chemoattractant protein 1 stimukates tumor necrosis and recruitment of macrophages into tumor in tumo-bearing mude mice: Increased granulocyte/macrophage progenitors in murine bone marrow." Exp. Hematol.3. 1035-1039 (1995)
[文献書誌] Sagawa,K.: "Production of IL-8 and the other cytokines by T cell clones established from the ocular fluid of patients with Behcet's disease." Ocular Immunol. Inflamm.3. 62-71 (1995)
[文献書誌] Fujioka,N.: "Preparation of specific antibodies against murine interleukin 1 receptor antagonist(IL-1 ra)and the establishment of IL-1 ra as endogenous regulator of bacteria-induced fulminant hepatitis in mice." J. Leukocyte Biol.58. 90-98 (1995)
[文献書誌] Hirose,K.: "Chemokine gene transfer into tumor cells reduced tumorigenicity in vivo mediated through neutroophilic infiltrate." Brit. J. Cancer.72. 708-714 (1995)
[文献書誌] Sugiyama,Y.: "Chemokines in bronchoalveolar lavage fluid in summer-type hypersenitivity penumonitis." Eur. Respir. J.8. 1084-1090 (1995)
[文献書誌] Ikeda,N.: "Prevention of bacterial induced hepatocelluar necrosis in rabbits by an antibody to leukocyte integrin b2 with concomitant inhibition of cytokine production." Infect. Immun.63. 4812-4817 (1995)
[文献書誌] Nakashima,E.: "MCAF gene transfer enhances the metastatic capacity of mouse cachectic adenocarcinoma cell line." Pharmaceutical Res.12. 1598-1604 (1995)
[文献書誌] Zhang,Y.: "TNFa as a physiological regulator of hematopoietic progenitor cells: Increase of early hematopoietic progenitor cells in TNF-R55-1-mice in vivo and potent inhibition of progenitor cell proliferation by TNFa in vitro." Blood. 6. 2930-2937 (1995)
[文献書誌] Teranishi,Y.: "Increased spontaneous production of IL-8 in peripheral blood monocytes from the psoriatic patient: relation to focal infection and response to treatments." J. Dermatol. Science. 10. 8-15 (1995)
[文献書誌] Larsen,C.G.: "The delayed-type hypersensitivity reaction is dependent on IL-8. Inhibition of a tuberculin skin reaction by an anti-IL-8 monoclonal antibody." J. Immunol.155. 2151-2157 (1995)
[文献書誌] Kuno,K.: "Identification of an IkBa-associated protein kinase in a human cell line and determination of its phosphorylation sites on IkBa." J. Biol. Chem.270. 27914-27919 (1995)
[文献書誌] Xiu,Q.: "Bronchial hyperresposiveness and airway neutrophil accumulation induced by interleukin-8 and the effect of the thromboxane A2 antagonist S-1452 in guinea-pigs." Clin. Exp. Allergy.25. 51-59 (1995)
[文献書誌] Yamamoto,N.: "Regulatory mechanisms for production of interferon-g and TNF by anti-tumor T cells or macrophages in the tumor-bearing state." J. Immunol.154. 2281-2289 (1995)
[文献書誌] Jinquan,T.: "Recombinant human growth-regulated oncogene-a induces T lymphocyte chemotaxis." J. Immunol.155. 5359-5368 (1995)
[文献書誌] Inoue,H.: "Expression of cytokines and adhesion molecules in hemodialysis-associated amyloidosis" Nephrol. Dialysis Transplant.(in press).
[文献書誌] Wada,T.: "Monitoring urinary levels of monocyte chemotactic and activating factor(MCAF)reflects disease activity of lupus nephritis." Kidney Int.(in press).
[文献書誌] Su,S-b.: "Rapid secretion of intracellularly pre-stored interleukin-8 from rabbit platelets upon the activation." J. Leukocyte Biol.(in press).
[文献書誌] Mukaida,N.: "Novel insight into molecular mechanism of endotokxin shock: biochemical analysis of LPS receptor signaling in a cell-free system targeting NF-kB and regulation of cytokine production/action through inteann b2 in vivo." J. Leukocyte Biol.(in press).
[文献書誌] Nielsen,B.W.: "Macrophage-Pathogene Interactions" Marcel Dekker, 11 (1994)
[文献書誌] Harada,A.: "Ares-Sereno Symposia Publications" Challenges of Modern Medicine Vol.3, 6 (1994)
[文献書誌] Matsushima,K.: "Proceeding of IIIrd International Mochida Memorial Symposium" The Mochida Memorial Foundation for Medical and Pharmaceutical Research, 8 (1994)
[文献書誌] Okamoto,S.: "In the Chemokines Proceeding of IIIrd International Symposium of Chemotactic Cytokines" Plenum, 10 (1994)
[文献書誌] Murakami,S.: "Viral Hepatitis and Liver Disease." 4 (1994)
[文献書誌] Mukaida,N.: "In Leukocyte Typing V" Oxford University Press, 3 (1995)
[文献書誌] Morohashi,H.: "In Leukocyte Typing V" Oxford University Press, 3 (1995)
[文献書誌] Mukaida,N.: "Cytokines: interleukins and their receptors." Kluwer Academic Publishers(in press),
[文献書誌] Harada,A.: "In Growth factor and cytokines in health and disease." JAI press(in press),
[文献書誌] Harada,A.: "In ImmunoMethod on Chemokine" Academic press(in press),
[文献書誌] Harada,A.: "The Roles of Chemokines in Disease" R. G. Landes Company(in press),

1995 年度 実績報告書

IL8抗体のヒト型化とサイトカイン遺伝子調節因子NFkBを標的とした抗炎症剤開発

研究代表者

松島 綱治 金沢大学, がん研究所, 教授 (50222427)

研究成果

[文献書誌] Okamoto,S.-i.: "The interleukin-8 AP-1 and kB-like sites are genetic end targets of FK506-sensitive pathway accompanied by calcium mobilization" J. Biol. Chem.269. 8582-8589 (1994)

[文献書誌] Mukaida,N.: "Novel mechanism of glucocorticoid-mediated gene repression: Nuclear factor-kB is target for glucocorticoid-mediated interleukin 8 gene repression" J. Biol. Chem.269. 13289-13295 (1994)

[文献書誌] Nakano,Y: "Protection against lethal bacterial infection in mice by monocyte-chemotactic and -activating factor(MACF)." Infect. Immun.62. 377-383 (1994)

[文献書誌] Murakami,S.: "Transactivation of human hepatitis B virus X protein, HBx, operates through a mechanism distinct from protein kinase C and okadaic acid activation pathway." Virology. 199. 243-246 (1994)

[文献書誌] Asano,T.: "Liposomal muramyl tripeptide up-regulates interleukin-1 alpha, interuleukin-1 beta, tumor necrosis factor-alpha, interleukin-6 and interleukin-8 gene expression in human monocytes." J. Pharmacol. Exp. Ther.268. 1032-1039 (1994)

[文献書誌] Kuno,K.,: "Acid sphingomyelinase is not essential for the IL 1 and tumor necrosis factor receptor signaling pathway leading to NFkB activation." Int. Immunol.6. 1269-1272 (1994)

[文献書誌] Kuno,K.: "The IL 1 receptor signaling pathway" J. Leukocyte Biology. 56. 542-547 (1994)

[文献書誌] Endo,H.: "Experimental arthritis induced by continuous infusion of IL-8 into rabbit knee joints." Clin. Exp. Immunol.96. 31-35 (1994)

[文献書誌] Harada,A.: "Cloning of a cDNA encoding a mouse homolog of the interleukin-8 receptor." Gene. 142. 297-300 (1994)

[文献書誌] Deleuran,B.: "Localisation of interleukin 8 in the synovial membrane, cartilage-pannus junction and chondrocytes in rheumatoid arthritis. Scand." Scand. J. Rheumatol.23. 2-7 (1994)

[文献書誌] Asano,T.: "Liposome-encapsulated muramyl tripeptide up-regulates monocyte chemotactic and activating factor gene expression in human monocytes at the transcriptional and post-transcriptional levels." Cancer Immunology and Immunotherapy. 38. 16-22 (1994)

[文献書誌] Oliveira,I.C.: "Transcriptional inhibition of the interleukin-8 gene by interferon is mediated by the NF-kB site." Mol. Cell Biol.14. 5300-5308 (1994)

[文献書誌] Akahoshi,T.: "Essential involvement of interleukin-8 in neutrophil recruitment in rabbits with acute experimental arthritis induced by lipopolysaccharide and interleukin-1." Lymphokine Cytokine Res.13. 113-116 (1994)

[文献書誌] Itoh,R.: "Interleukin-8 in Behcet's Disease." J. Dermatology. 21. 397-404 (1994)

[文献書誌] Mizuno,K.: "Spontaneous production of interleukin-8 by human lung cancer cells and its augmentation by tumor necrosis factor alpha and interleukin-1 at protein and mRNA levels." Oncology. 51. 467-471 (1994)

[文献書誌] Ito,A.: "Suppression of interleukin 8 production by progesterone in rabbit uterine cervix." Biochem. J.301. 183-186 (1994)

[文献書誌] Kasahara,K.: "Selective expression of monocyte chemotactic and activating factor/monocyte chemoattractant protein 1 in human blood monocytes by mycobacterium tuberculosis." J. Infectious Dis.170. 1238-1247 (1994)

[文献書誌] Murayama,T.: "Elevated cytokine levels in synovial fluid of rheumatoid arthritis correlates with the presence of cytomegalovirus genome." Autoimmunity. 17. 333-337 (1994)

[文献書誌] Wada,T.: "Detection of urinary interleukin-8 in glomerular diseases." Kidney Int.46. 455-460 (1994)

[文献書誌] Nakamoto,Y.: "Detection of the putative E2 protein of hepatitis C virus in human liver." J. Med. Virology. 42. 374-379 (1994)

[文献書誌] Wada,T.: "Appearance of interleukin-8 in the Urine Predicts Acute rejection of Renal Transplantation." Nephrol. Dial. Transplant.9. 874-875 (1994)

[文献書誌] Wada,T.: "Prevention of proteinuria in acute immune complex-mediated glomerulonephritis by an antibody against interleukin 8." J. Exp. Med.180. 1135-1140 (1994)

[文献書誌] Murayama,T.: "Enhancement of human cytomegalovirus replication in human lung fibroblast cell line by interleukin 8." J. Virol.68. 7582-7584 (1994)

[文献書誌] Mukaida,N.: "Molecular mechanism of interleukin 8(IL-8)gene expression." J. Leukocyte Biology. 56. 554-558 (1994)

[文献書誌] Harada,A.: "Essential involvement of interleukin 8(IL 8)in acute inflammation." J. Leukocyte Biology. 56. 559-564 (1994)

[文献書誌] Oishi,K.: "Role of interleukin-8(IL-8)and an inhibitory effect of erythromycin on IL-8 release in the airways of patients with chronic airway diseases." Infect. Immun.62. 4145-4152 (1995)

[文献書誌] Ko,Y.-C.: "Specific elevation of interleukin-8 levels in peritoneal dialysates of patients on continous ambulatory peritoneal dialysis with peritonitis." J. Clin. Pathol.48. 115-119 (1995)

[文献書誌] Morohashi,H.: "Expression of both types of human interleukin 8(IL-8)receptors on mature neurtophils, monocyts, and CD16+lymphocytes." J. Leukocyte Biol.57. 180-187 (1995)

[文献書誌] Yano,S.: "Differential effects of anti-inflammatory cytokines(IL-4,IL-10,and IL-13)on tumorcidal and chemotactic properties of human monocytes induced by monocyte chmotactic and activating factor(MCAF)." J. Leukcyte Biol.57. 303-309 (1995)

[文献書誌] Yasumoto,K.: "Molecular analysis of cytokine network involved in causing cachexia in colon 26 adenocarcinoma-bearing mice." Cancer Res.55. 921-927 (1995)

[文献書誌] Ishikawa,Y.: "Establishment of lipopolysaccharide-dependent nuclear factor-kB activation in a cell-free system." J. Biol. Chem.270. 4158-4164 (1995)

[文献書誌] Watanabe,S.-i.: "Prevention of endotoxin shock by an antibody against leukocyte integrin b2 through inhibiting production and action of tumor necrosis factor." Intl. Immunol.7. 1037-1046 (1995)

[文献書誌] Hoshino,Y.: "Monocyte chemoattractant protein 1 stimukates tumor necrosis and recruitment of macrophages into tumor in tumo-bearing mude mice: Increased granulocyte/macrophage progenitors in murine bone marrow." Exp. Hematol.3. 1035-1039 (1995)

[文献書誌] Sagawa,K.: "Production of IL-8 and the other cytokines by T cell clones established from the ocular fluid of patients with Behcet's disease." Ocular Immunol. Inflamm.3. 62-71 (1995)

[文献書誌] Fujioka,N.: "Preparation of specific antibodies against murine interleukin 1 receptor antagonist(IL-1 ra)and the establishment of IL-1 ra as endogenous regulator of bacteria-induced fulminant hepatitis in mice." J. Leukocyte Biol.58. 90-98 (1995)

[文献書誌] Hirose,K.: "Chemokine gene transfer into tumor cells reduced tumorigenicity in vivo mediated through neutroophilic infiltrate." Brit. J. Cancer.72. 708-714 (1995)

[文献書誌] Sugiyama,Y.: "Chemokines in bronchoalveolar lavage fluid in summer-type hypersenitivity penumonitis." Eur. Respir. J.8. 1084-1090 (1995)

[文献書誌] Ikeda,N.: "Prevention of bacterial induced hepatocelluar necrosis in rabbits by an antibody to leukocyte integrin b2 with concomitant inhibition of cytokine production." Infect. Immun.63. 4812-4817 (1995)

[文献書誌] Nakashima,E.: "MCAF gene transfer enhances the metastatic capacity of mouse cachectic adenocarcinoma cell line." Pharmaceutical Res.12. 1598-1604 (1995)

[文献書誌] Zhang,Y.: "TNFa as a physiological regulator of hematopoietic progenitor cells: Increase of early hematopoietic progenitor cells in TNF-R55-1-mice in vivo and potent inhibition of progenitor cell proliferation by TNFa in vitro." Blood. 6. 2930-2937 (1995)

[文献書誌] Teranishi,Y.: "Increased spontaneous production of IL-8 in peripheral blood monocytes from the psoriatic patient: relation to focal infection and response to treatments." J. Dermatol. Science. 10. 8-15 (1995)

[文献書誌] Larsen,C.G.: "The delayed-type hypersensitivity reaction is dependent on IL-8. Inhibition of a tuberculin skin reaction by an anti-IL-8 monoclonal antibody." J. Immunol.155. 2151-2157 (1995)

[文献書誌] Kuno,K.: "Identification of an IkBa-associated protein kinase in a human cell line and determination of its phosphorylation sites on IkBa." J. Biol. Chem.270. 27914-27919 (1995)

[文献書誌] Xiu,Q.: "Bronchial hyperresposiveness and airway neutrophil accumulation induced by interleukin-8 and the effect of the thromboxane A2 antagonist S-1452 in guinea-pigs." Clin. Exp. Allergy.25. 51-59 (1995)

[文献書誌] Yamamoto,N.: "Regulatory mechanisms for production of interferon-g and TNF by anti-tumor T cells or macrophages in the tumor-bearing state." J. Immunol.154. 2281-2289 (1995)

[文献書誌] Jinquan,T.: "Recombinant human growth-regulated oncogene-a induces T lymphocyte chemotaxis." J. Immunol.155. 5359-5368 (1995)

[文献書誌] Inoue,H.: "Expression of cytokines and adhesion molecules in hemodialysis-associated amyloidosis" Nephrol. Dialysis Transplant.(in press).

[文献書誌] Wada,T.: "Monitoring urinary levels of monocyte chemotactic and activating factor(MCAF)reflects disease activity of lupus nephritis." Kidney Int.(in press).

[文献書誌] Su,S-b.: "Rapid secretion of intracellularly pre-stored interleukin-8 from rabbit platelets upon the activation." J. Leukocyte Biol.(in press).

[文献書誌] Mukaida,N.: "Novel insight into molecular mechanism of endotokxin shock: biochemical analysis of LPS receptor signaling in a cell-free system targeting NF-kB and regulation of cytokine production/action through inteann b2 in vivo." J. Leukocyte Biol.(in press).

[文献書誌] Nielsen,B.W.: "Macrophage-Pathogene Interactions" Marcel Dekker, 11 (1994)

[文献書誌] Harada,A.: "Ares-Sereno Symposia Publications" Challenges of Modern Medicine Vol.3, 6 (1994)

[文献書誌] Matsushima,K.: "Proceeding of IIIrd International Mochida Memorial Symposium" The Mochida Memorial Foundation for Medical and Pharmaceutical Research, 8 (1994)

[文献書誌] Okamoto,S.: "In the Chemokines Proceeding of IIIrd International Symposium of Chemotactic Cytokines" Plenum, 10 (1994)

[文献書誌] Murakami,S.: "Viral Hepatitis and Liver Disease." 4 (1994)

[文献書誌] Mukaida,N.: "In Leukocyte Typing V" Oxford University Press, 3 (1995)

[文献書誌] Morohashi,H.: "In Leukocyte Typing V" Oxford University Press, 3 (1995)

[文献書誌] Mukaida,N.: "Cytokines: interleukins and their receptors." Kluwer Academic Publishers(in press),

[文献書誌] Harada,A.: "In Growth factor and cytokines in health and disease." JAI press(in press),

[文献書誌] Harada,A.: "In ImmunoMethod on Chemokine" Academic press(in press),

[文献書誌] Harada,A.: "The Roles of Chemokines in Disease" R. G. Landes Company(in press),

1995 年度実績報告書

松島綱治金沢大学, がん研究所, 教授 (50222427)