ෘ↢ഭ௛⑼ቇ⎇ⓥ⾌⵬ഥ㊄㧔ሶߤ߽ኅᐸ✚ว⎇ⓥ੐ᬺ㧕ಽᜂ⎇ⓥႎ๔ᦠಽᜂ⺖㗴 㧦 )TCPWN[UKPߣᵹ↥ߦ㑐ߔࠆ⎇ⓥ                ⎇ⓥઍ⴫⠪ 㥲⮮ ṑ  ንጊᄢቇ↥⑼ᇚੱ⑼ቇᢎ᝼                  ਛፉ ᓆବ ንጊᄢቇ↥⑼ᇚੱ⑼ቇഥᢎ
⎇ⓥⷐᣦ
6 ⚦⢩߹ߚߪ 0- ⚦⢩ߩ↥↢ߔࠆ⚦⢩்ኂᕈⰮ⊕㧔․ߦ )TCPWN[UKP ⚦⢩்ኂᕈߦࠃࠆᵹ↥⺃ዉࡔࠞ࠾࠭ࡓࠍ⸃᣿ߔࠆߎߣߦࠃࠅ‫ߢ߹߹޿ޔ‬ਇ᣿ߢ޽ߞߚਇ⢒∝⺃ዉ࿃ሶࠍ޽߈ࠄ߆ߦߔࠆ‫ޕ‬㧭㧚⎇ⓥ⋡⊛ߎࠇ߹ߢߦਇ⢒∝ߩේ࿃ߣ޿ࠊࠇࠆ߽ߩߪᄙᢙႎ๔ߐࠇߡ޿ࠆ߇‫߽ᦨ߇ࠇߤޔ‬㊀ⷐ߆ߣ޿߁ὐߦ߅޿ߡߪᧂߛਇ᣿ߥὐ߫߆ࠅߢ޽ࠆ‫ߢ߹ࠇߎޔߢߎߘޕ‬ਇ᣿ߢ޽ߞߚᵹ↥ߩታⴕ࿃ሶࠍหቯߒ‫ࠄࠇߘޔ‬ታⴕ࿃ሶߩᵴᕈൻࠍ⺞ᢛߔࠆේ࿃ࠍหቯߔࠆߎߣ߇‫ޔ‬     ਇ⢒∝ߩ⸃᣿ߦߟߥ߇ࠆߣ⠨߃‫⎇ޔ‬ⓥࠍ㐿 ᆎߒߚ‫ޕ‬ߎࠇ߹ߢ⣕⪭⤑࡝ࡦࡄ⃿ߪ‫ޔ‬⢝ఽ⚦⢩߳ߩ఺∉ኡኈ╬ߩᯏ᭴ߦࠃࠅ⢝⋚ࠍᒻᚑߒ‫ޔ‬ᅧᆼ⛽ᜬߦᱜߩᓎഀࠍᨐߚߔߣ⠨߃ࠄࠇߡ߈ߚ‫⚦ࠄࠇߘޕ‬⢩ߩᵴᕈൻ߇‫ޔ‬⢝ఽ↱᧪⚦⢩ߢ޽ࠆ⛐Ძᄖᩕ㙃⤑⚦⢩ߩឃ㒰㧔ߟ߹ࠅᵹ↥⺃ዉ㧕ߦ㑐ਈߒߥ޿߆ࠍᬌ⸛ߒߚ‫ޕ‬ 㧮㧚⎇ⓥᣇᴺ⣕⪭⤑࡝ࡦࡄ⃿ߪ  ㅳ೨ᓟߦ߅޿ߡታᣉߐࠇߚੱᎿᵹ↥ᚻⴚࠍታᣉߐࠇߚᖚ⠪ ฬ߅ࠃ߮ᵹ↥ᚻⴚࠍታᣉߒߚ  ฬ߆ࠄ‫ޔ‬⺑᣿ߣหᗧ㧔ࠗࡦࡈࠜ࡯ࡓ࠼࡮ࠦࡦ࠮ࡦ࠻㧕ࠍᓧߚ਄ߢᬌ૕ࠍណขߒߚ‫ޕ‬    㧔୶ℂ㕙߳ߩ㈩ᘦ㧕⎇ⓥ⚿ᨐߪ‫⚿ޔ‬ᨐߩߺࠍ౏⴫ߒ‫ޔ‬ኻ⽎⠪ߩ୘ੱᖱႎߩṳᵨ߇⿠ߎࠄߥ޿ࠃ߁ߦ㈩ᘦ
     ߒߚ‫ޕ‬    
   㧯㧚⎇ⓥ⚿ᨐ  㧚 ⣕⪭⤑ߦ߅ߌࠆ⚦⢩்ኂᕈ㗰☸Ⱞ⊕ߩ⊒⃻ ߩ ᬌ ⸛ 㧦 )TCPWN[UKP)TCP\[OG$2GTHQTKP ߩ⊒⃻ࠍᵹ↥ᬌ૕߅ࠃ߮ᱜᏱᅧᆼᬌ૕ߦߡᬌ⸛ߔࠆߣ‫ޔ‬ၮᐩ⣕⪭⤑ߦ߅ߌࠆ )TCPWN[UKP㧔)T㧕㓁ᕈ⚦⢩ᢙߪᵹ↥଀ߢᱜᏱᅧᆼߦᲧߒ᦭ᗧߦჇടߒߡ޿ߚ৻ᣇߢઁߩ்ኂᕈ㗰☸࠲ࡦࡄࠢߢ޽ࠆ2GTHQTKP)TCP\[OG$ ߩ⊒⃻ߦߪ᦭ᗧᏅࠍ⹺߼ߥ߆ߞߚ㧞㧚⣕⪭⤑࡝ࡦࡄ⃿ߦ߅ߌࠆ )TCPWN[UKP 㓁ᕈ⚦⢩ߩᬌ⸛㧦)T ⊒⃻⚦⢩ࠍࡈࡠ࡯ࠨࠗ࠻ࡔ࠻࡝࡯ᴺߦ߅޿ߡᬌ⸛ߒߚߣߎࠈ%&DTKIJV0-㧔%& 㧕⚦⢩ߦߩߺ )T ߪᒝ⊒⃻ߒߡ߅ࠅ‫ޔ‬6 ⚦⢩ߦ߶ߣࠎߤ )T ߩ⊒⃻ࠍ⹺߼ߥ߆ߞߚ‫ߚ߹ޕ‬ᵹ↥଀ߩ )T 㓁ᕈ %& ⚦⢩ߪᱜᏱᅧᆼߣᲧセߒߡ᦭ᗧߦ㜞߆ߞߚ‫⥝ߦࠄߐޕ‬๧ᷓ޿ߎߣߦੑ㊀఺∉ᨴ⦡ߦ߅޿ߡ‫ޔ‬ᵹ↥଀ߢ⛐Ძᄖᩕ㙃⤑㧔EVT㧕⚦⢩ߩᩭౝߦ Gr ⊒⃻ࠍ⹺߼,ߎࠇࠄߩ⚦⢩߇ࠕࡐ࠻࡯ࠪࠬߦ㒱ߞߡ޿ߚ'86 ߩ O40# ⊒⃻࡟ࡌ࡞ߦ߅޿
ߡ‫)ޔ‬T ⊒⃻ߪ⹺߼ࠄࠇߥ߆ߞߚߎߣࠃࠅ‫ޔ‬)T 㓁ᕈ %& ⚦⢩߇ '86 ߦ )T ࠍዉ౉ߒߡ޿ࠆ੐߇ផ᷹ߐࠇߚ‫ ߢߎߘޕ‬Ap ⺃ዉߣGr ߩᩭౝ⒖ⴕߩ㑐ଥࠍ⸃᣿ߔࠆߚ߼ invitro ߦߡ +. ೝỗߒߚ⣕⪭⤑࡝ࡦࡄ⃿߆ࠄ %& ⚦⢩ࠍಽ㔌ߒ'86 ࠮࡞࡜ࠗࡦߣ౒ၭ㙃ࠍⴕߞߚ‫ߩߘޕ‬ታ㛎⚿ᨐ߆ࠄ‫'ޔ‬86⚦⢩ౝߢ )T ߩᩭౝ⒖ⴕ߇ⷰኤߐࠇߚߟ߹
ࠅ‫ޔ‬ታ㛎⊛ߦ߽ %& ⚦⢩߆ࠄ '86 ߦ )T߇ዉ౉ߐࠇ‫) ߩߘޔ‬T ߇ᩭౝ⒖ⴕߔࠆߎߣ
߇⸽᣿ߐࠇߚ‫ޕ‬119
120

߹ߚ‫ ߩߎޔ‬0- ⚦⢩߆ࠄಽᴲߐࠇߚ )T ߩ '86
߳ߩ⒖ⴕߪ⚦⢩ធ⸅ ࠻࡜ࡦࠬ࠙ࠚ࡞ታ㛎 ߅ࠃ߮ 2GTHQTKP ଐሽᕈ 2GTHQTKP ᛥ೙೷ಣℂߦࠃࠅ )T ߩ '86 ߳ߩ⒖ⴕ߇ⷰኤߐ
ࠇߥߊߥࠆ ߢ޽ࠆߎߣ߇ಽ߆ߞߚ‫ࠄߐޕ‬
ߦ'86 ⚦⢩ߦ )(2 Ⲣว )T ࠍᒝ⊒⃻ߐߖߚߣߎࠈ)T ߪ⚦⢩⾰߆ࠄᩭౝߦ⒖ⴕߒ‫ߘޔ‬ࠇߣ౒ߦ #R ߩჇടࠍ⹺߼ߚㅊടߣߒߡ)T ߩ⚦⢩ౝ⒖േࡔࠞ࠾࠭ࡓߩ⸃᣿ߩߚ߼ ‫() ޔ‬2Z ಽ ሶ ࠍ ⚿ ว ߒ ߚ)(2Z)TCPWN[UKP ⊒⃻ࡌࠢ࠲࡯ࠍ૞ᚑߒߚ‫()ޔߪࠇߎޕ‬2Z ߪಽሶ㊂ߩ㑐ଥ߆ࠄᩭౝߦන⚐᜛ᢔߢ߈ߥ޿ߎߣ߇ಽ߆ߞߡ޿ࠆ‫'ࠄ߇ߥߒ߆ߒޕ‬86 ⚦⢩ౝߦዉ౉ߐࠇߚ)(2Z)TCPWN[UKP ߪᩭౝߦ㓸Ⓧߔࠆߎߣࠍᚒ‫⸽ߪޘ‬᣿ߒߚ‫)ࠅ߹ߟޕ‬T ߪ⢻േ⊛ߦ
ᩭౝߦ⒖ⴕߔࠆߎߣߢࠕࡐ࠻࡯ࠪࠬ⺃ዉߦ㑐ਈߔࠆߎߣ߇␜ߐࠇߚ‫ޕ‬㧰㧚⠨ኤ੹࿁ߩ⚿ᨐࠃࠅ‫ޔ‬⣕⪭⤑࡝ࡦࡄ⃿ߦ߅ߌࠆⴊ▤ᒻᚑߦ㊀ⷐߥᓎഀࠍᨐߚߔߣ⠨߃ࠄࠇߡ߈ߚ 0- ⚦⢩㧔Უ૕↱᧪㧕߇‫⋥ޔ‬ធ⛐Ძᄖᩕ㙃⤑⚦⢩㧔⢝ఽ↱᧪㧕ࠍ⋥ធ᡹᠄‫ޔ‬ࠕࡐ࠻࡯ࠪࠬࠍ⺃ዉߔࠆߎߣࠍ਎⇇ߦవ㚟ߌߡႎ๔ߒߚ‫ߪ⽎⃻ߩߎޔߚ߹ޕ‬ᵹ↥߇⺃ዉߐࠇࠆ㊀ⷐߥᯏ᭴ߢ޽ࠆߣផቯߐࠇ
ࠆ‫ߢ߹ࠇߎޔࠄߥߗߥޕ‬ᵹ↥ߩਥߥේ࿃ߩ߭ߣߟߣߐࠇࠆᨴ⦡૕⇣Ᏹࠍ⹺߼ࠆ∝଀ߩߺߥࠄߕ‫⇣ߩߘޔ‬Ᏹࠍ⹺߼ߥ޿∝଀ߦ߅޿ߡ߽ห᭽ߦߎߩᯏ᭴߇௛޿ߡ޿ࠆ੐߇
⏕⹺ߐࠇߚߚ߼ߢ޽ࠆ‫ޔࠅ߹ߟޕ‬૗ࠄ߆ߩ⺃ዉ࿃ሶ߇ 0- ⚦⢩ߩᵴᕈൻࠍᒁ߈⿠ߎߒ
ᵹ↥ࠍ⺃ዉߔࠆߣ⠨߃ࠄࠇࠆࠊߌߢ޽ࠆ‫ޕ‬ߎߩ⚿ᨐߦട߃‫ߦߢ߹ࠇߎޔ‬ᚒ‫ߪޘ‬6J6J ࡃ࡜ࡦࠬߩⷰὐ߆ࠄ 6J ᦭ᗧߥ⁁ᴫ߇ᵹ↥ߦ㑐ਈߔࠆߎߣ‫ޔ‬ᵹ↥∝଀ⴊᷡߦ߅ߌࠆ )TCPWN[UKP Ớᐲ߇ᱜᏱᅧᆼ଀ߣᲧセߒ㜞୯ࠍ␜ߔߎߣࠍႎ๔ߒߡ߈ߚ‫ߩߎޕ‬ߎߣߪ‫ߢ߹ࠇߎޔ‬ႎ๔ߐࠇߡ߈ߚᵹ↥ߩ⺃ዉ࿃ሶߣߐࠇࠆ߽ߩ߇‫ޔ‬0- ⚦⢩ߦ߅ߌࠆ)TCPWN[UKP ߩ⊒⃻ߦᓇ㗀ߒ߁ࠆ߆‫ޔ‬6J ᦭ᗧߥ⁁ᴫࠍ⺃ዉߒ߁ࠆ߆ߥߤ੹߹ߢߦߥ߆ߞߚਇ⢒∝࿃ሶߩᬌᩏᴺߣߥࠅ߁ࠆߣ⠨߃ࠄࠇ‫⥃ޔ‬ᐥᔕ↪߽฽߼⥃ᐥ⚿ᨐߣኻᲧߐߖߡ޿߈ߚ޿ߣ⠨߃ߡ޿ࠆ‫ޕ‬⥄ὼᵹ↥䈪䈲䇮NK⚦⢩䈏Granulysin䉕੺䈚䈩
EVT⚦⢩䈮Apoptosis䉕⺃ዉ䈜䉎
Our proposal of novel pathwayactivation
 Granulysin pathway 

 D  
Fas-FasL pathway
TNF-D pathway(Mor G; Matsuo H)(Huppertz B)㧱㧚⚿⺰  ⚦⢩㓚ኂᕈ㗰☸Ⱞ⊕ߢ޽ࠆ)TCPWN[UKP ߪ Უ૕↱᧪ߩ⣕⪭⤑0-⚦⢩߆ࠄ‫ޔ‬⢝ఽ↱᧪⚦⢩ߢ޽ࠆ⛐Ძᄖᩕ㙃⤑⚦⢩ߦಽᴲߐࠇ‫⛐ޔ‬Ძᄖᩕ㙃⤑⚦⢩ߦࠕࡐ࠻࡯ࠪࠬࠍ⺃ዉߔࠆ‫ߩߎޕ‬ᯏ᭴ߪ‫ޔ‬ᵹ↥⺃ዉߦ㊀ⷐߥᓎഀࠍᨐߚߔ‫ޕ‬㧲㧚ஜᐽෂ㒾ᖱႎ  ․ߦߥߒ㧳㧚⎇ⓥ⊒⴫⺰ᢥ⊒⴫  0CMCUJKOC#5JKQ\CMK#/[QLQ5+VQ/6CVGOCVUW/5CMCK/6CMCOQTK⥄ὼᵹ↥䈪䈲䇮NK⚦⢩䈏Granulysin䉕੺䈚䈩;1ICYC-0CICVC-5CKVQ5EVT⚦⢩䈮Apoptosis䉕⺃ዉ䈜䉎
Our proposal of novel pathway)TCPWN[UKPRTQFWEGFD[WVGTKPGPCVWTCN
activation
Granulysin pathway
MKNNGTEGNNUKPFWEGUCRQRVQUKUQHGZVTCXKNNQWUVTQRJQDNCUVUKPURQPVC PGQWUCDQTVKQP#OGTKECP,QWTPCNQH
2CVJQNQI[  
ቇળ⊒⴫D  0CMCUJKOC#5JKQ\CMK#/[QLQ5+VQ/6CVGOCVUW/5CKVQ5&GEKFWCN
0CVWTCN-KNNGTEGNNFGTKXGFITCPWN[UKPJUDQXO\VLQKPFWEGUCRQRVQUKUQHGZVTCXKNNQWUVTQRJQDNCUVKPOKUECTTKCIGVJ+PVGT
PCVKQPCN(GFGTCVKQPQH2NCEGPVC#UUQEKCVKQPU/GGVKPI5GRVGODGT
5GIICW%CUVNG#WUVTKC ਛፉᓆବႮፒ᦭ብદ⮮ታ㚅┙᧻⟤᮸ሶ᣿ᤊ㗇᥍㥲⮮ṑᵹ↥∝଀ߦ߅޿ߡ‫)ޔ‬TCPWN[UKP㓁ᕈ0-⚦⢩ߪ'ZVTCXKNNQWUVTQRJQDNCUV '86 ࠍࠕࡐ࠻࡯ࠪࠬߦ㒱ࠄߖࠆ╙࿁ᣣᧄ⢝⋚ቇળቇⴚ㓸ળᐕ᦬ᣣᣣᵿ᧻㧚 ਛፉᓆବႮፒ᦭ብ᣿ᤊ㗇᥍દ⮮ታ㚅┙᧻⟤᮸ሶ㥲⮮ṑ⣕⪭⤑0-⚦⢩↱᧪)TCPWN[UKPߪ⛐Ძᄖ࠻ࡠࡎࡉ࡜ࠬ࠻ߦࠕࡐ࠻࡯ࠪࠬࠍ⺃ዉߒ‫ޔ‬ᵹ↥⺃ዉߦ㑐ਈߔࠆ㧚╙࿁ᣣᧄ↢ᱺ఺∉ቇળ✚ળ࡮ቇⴚ㓸ળᐕ᦬ᣣንጊ㧚㧴㧚⍮⊛⽷↥ᮭߩ಴㗿࡮⊓㍳⁁ᴫ  㧔੍ቯࠍ฽߻‫ޕ‬㧕․⸵ขᓧ ߥߒታ↪ᣂ᩺⊓㍳ ߥߒߘߩઁ    ߥߒ 121 ⎇ⓥᚑᨐߩೀⴕߦ㑐ߔࠆ৻ⷩ⴫  㔀⹹ ⊒⴫⠪᳁ฬ ⺰ᢥ࠲ࠗ࠻࡞ฬ ⊒⴫⹹ฬ0CMCUJKOC#5JKQ\CMK# )TCPWN[UKPRTQFWEGF
/[QLQ5 D[WVGTKPGPCVWTCN
+VQ/ MKNNGTEGNNU #OGTKECP6CVGOCVUW/ KPFWEGUCRQRVQUKU
5CMCK/ QHGZVTCXKNNQWU ,QWTPCNQH
6CMCOQTK; VTQRJQDNCUVUKP 2CVJQNQI[1ICYC- URQPVCPGQWUCDQT0CICVC- VKQP5CKVQ5122 Ꮞภ ࡍ࡯ࠫ ಴ ᐕ