áImmunotoxicology Å‘Oüâ

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2002; 7(2), 12-13


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@–Ɖu’S“–×–E‚ªŠO‚©‚ç—lX‚ÈŽhŒƒ‚ðŽó‚¯‘BA•ª‰»‚ ‚é‚¢‚̓Aƒ|ƒg[ƒVƒX‚È‚Ç‚ÉŽŠ‚é‰ß’ö‚É‚¨‚¢‚āAŠOŠEŽhŒƒ‚ª×–E“àƒVƒOƒiƒ‹“`’B‹@\‚ð‰î‚µ‚ÄŠj‚É“`’B‚³‚ꂽ‚Ì‚¿ŽíX‚̈â“`Žq‚ª”­Œ»‚³‚ê‚邱‚Æ‚ª•K—v‚Å‚ ‚é(}1)B‚µ‚½‚ª‚Á‚āA–Ɖu“Ő«•¨Ž¿‚É‚æ‚Á‚čזE“àƒVƒOƒiƒ‹“`’B‚ª‰e‹¿‚ðŽó‚¯‚é‚ƁA–Ɖu’S“–×–E‚̐³í‚È‹@”\‚ª‘¹‚È‚í‚ê‚邱‚Æ‚É‚È‚éB‹ß”NA–Ɖu’S“–×–E“à‚̃VƒOƒiƒ‹“`’B‹@\‚ªŽŸX‚Æ–¾‚ç‚©‚É‚³‚ê‚Ä‚«‚Ä‚¢‚邪A–{e‚ł͖Ɖu“Ő«‚Ì”­Œ»‹@˜‚ðl‚¦‚邤‚¦‚ōזE“à‚̃VƒOƒiƒ‹“`’BŒo˜H‚ɂ‚¢‚čl‚¦‚Ä‚Ý‚½‚¢B

@Ž÷ó×–E‚Ȃǂ̍RŒ´’ñŽ¦×–E‚É‚æ‚Á‚ÄŽæ‚荞‚܂ꂽRŒ´ƒ^ƒ“ƒpƒNŽ¿‚̓yƒvƒ`ƒh‚É‚Ü‚Å•ª‰ð‚³‚ꂽ‚Ì‚¿ÅI“I‚É‚ÍŽå—v‘gD“K‡«RŒ´(major histocompatibility antigen; MHCRŒ´)ã‚É’ñŽ¦‚³‚ê‚é‚悤‚ɂȂ邪AT×–E‚Í‚±‚̍RŒ´‚ðŠOŠEŽhŒƒ‚Æ‚µ‚ÄŽó—eE”FŽ¯‚µ‚½‚Ì‚¿ÅI“I‚È•\Œ»Œ`‚Æ‚µ‚ÄŽíX‚̃TƒCƒgƒJƒCƒ“‚ð”­Œ»‚·‚é‚悤‚É‚È‚é(}2)B‚±‚̍RŒ´ŽhŒƒ‚ðÅ‰‚ÉŽó—e‚·‚é‚Ì‚ªŒ¾‚¤‚Ü‚Å‚à‚È‚­T×–EŽó—e‘Ì(T cell receptor; TCR)‚Å‚ ‚éB‚Ü‚½AB×–E‚É‚¨‚¢‚Ä‚à×–E–Œã‚É‚ ‚é–ƉuƒOƒƒuƒŠƒ“‚ªB×–EŽó—e‘Ì(B cell receptor; BCR)‚Æ‚µ‚Ä‹@”\‚µA’¼ÚRŒ´•ªŽq‚Ì•\–Ê‚É‚ ‚éRŒ´Œˆ’èŠî‚Æ“ÁˆÙ“I‚ÉŒ‹‡‚µŽhŒƒ‚ðŽó—e‚·‚邱‚Æ‚É‚È‚éBTCRABCR‚Í‚Æ‚à‚É‚»‚̍זE“à—̈æ‚Ƀ`ƒƒVƒ“ƒLƒi[ƒ[(protein tyrosine kinase; PTK)ƒhƒƒCƒ“‚ðŽ‚½‚¸A‚»‚ê‚݂̂ł̓ŠƒKƒ“ƒh‚ð”FŽ¯‚µ‚Ä‚àƒVƒOƒiƒ‹‚ª“`’B‚³‚ê‚È‚¢B‚»‚Ì‚½‚ßTCR‚âBCR‚́A×–E“à—̈æ‚ÉITAM(immunoreceptor tyrosine-based activation motif)‚ƌĂ΂ê‚éƒVƒOƒiƒ‹“`’B‚É•K{‚̃Aƒ~ƒmŽ_”z—ñ‚ð—L‚·‚éƒTƒuƒ†ƒjƒbƒg‚Æ‚Ì•¡‡‘Ì‚Æ‚µ‚Ä”­Œ»‚µ‚Ä‚¢‚éB



@T×–E(}2)‚Å‚ÍTCR‚ªMHCRŒ´ã‚̍RŒ´ƒyƒvƒ`ƒh‚ð”FŽ¯‚·‚é‚Æ“¯Žž‚ɁAƒwƒ‹ƒp[T×–E‚̏ꍇCD4‚ªMHCƒNƒ‰ƒX‡U•ªŽq‚ɁA‚Ü‚½×–EŠQ«T×–E‚̏ꍇ‚ÍCD8‚ªMHCƒNƒ‰ƒX‡T•ªŽq‚É‚»‚ꂼ‚ꌋ‡‚µTCR‚ÆMHC•¡‡‘Ì‚ÌŒ‹‡‚ðˆÀ’艻‚³‚¹‚é1C2)B‚»‚ÌŒãA×–E“à‚Å‚Í—lX‚ȃ^ƒ“ƒpƒNŽ¿‚̃Šƒ“Ž_‰»‚ª‹N‚±‚邱‚Æ‚É‚È‚éB‚Ü‚¸ACD4/8‚̍זE“àƒhƒƒCƒ“‚ɉ‚·‚éLck(Srcƒtƒ@ƒ~ƒŠ[PTK)‚ªŠˆ«‰»‚³‚êATCR‚Æ•¡‡‘Ì‚ðŒ`¬‚µ‚Ä‚¢‚éCD3‚ÌITAM‚ªƒ`ƒƒVƒ“ƒŠƒ“Ž_‰»‚ðŽó‚¯‚éB‚»‚̃Šƒ“Ž_Šî‚ÉZAP-70(Sykƒtƒ@ƒ~ƒŠ[PTK)‚ª‚»‚Ì•ªŽq“à‚É—L‚·‚éSH2ƒhƒƒCƒ“‚ð‰î‚µ‚ĉ‚µA‚»‚ê‚É‚æ‚èZAP-70‚ÍLck‚©‚烊ƒ“Ž_‰»‚ðŽó‚¯ƒLƒi[ƒ[‚Æ‚µ‚ÄŠˆ«‰»‚µX‚ɉº—¬‚̊‚ðƒŠƒ“Ž_‰»‚µŠˆ«‰»ƒVƒOƒiƒ‹‚ð“`‚¦‚éBZAP-70‚̊‚Æ‚È‚é‚Ì‚ÍLAT(linker for activation of T cell)‚âSLP-76‚Ȃǂ̃Aƒ_ƒvƒ^[•ªŽq‚Å‚ ‚éBSLP-76‚ÍSH2ƒhƒƒCƒ“‚ð‰î‚µ‚ÄVav‚Ɖ‚µRac/JNK(c-Jun N-terminal kinase)Œo˜H‚ðŠˆ«‰»‚µ‚Ä“]ŽÊˆöŽqAP-1(activator protein-1AFos‚ÆJun‚̃wƒeƒƒ_ƒCƒ}[)‚̃Šƒ“Ž_‰»‚ð—U“±‚·‚éBˆê•ûLAT‚Í‘½‚­‚̃`ƒƒVƒ“ŽcŠî‚ð—L‚µAƒŠƒ“Ž_‰»‚É‚æ‚èPLC(phospholipase C)‚âGrb2‚È‚Ç‚ÆŒ‹‡‚µ‚±‚ê‚番Žq‚ð×–E–Œ‚Ɉڍs‚³‚¹‚éBLAT‚ÆGrb2‚ªŒ‹‡‚·‚é‚ƁAGrb2“à‚ÌSH3ƒhƒƒCƒ“‚ð‰î‚µ‚ÄSos‚ª‰ï‡‚µARas/MAPK(mitogen-activated protein kinase)Œo˜H‚ªŠˆ«‰»‚³‚ê‚éBMAPK‚ÍFos‚Ì“]ŽÊ‚ð—U“±‚·‚éB‚Ü‚½APLC‚ÌŠˆ«‰»‚É‚æ‚菬–E‘Ì‚©‚çCa2+•úo‚ªˆø‹N‚³‚ê‚éB×–E“àCa2+”Z“x‚̏㏸‚É‚æ‚èƒzƒXƒtƒ@ƒ^[ƒ[‚Å‚ ‚éCN(calcineurin)‚ªŠˆ«‰»‚³‚êA×–EŽ¿“à‚ɃŠƒ“Ž_‰»ó‘Ô‚Å‘¶Ý‚·‚é“]ŽÊˆöŽqNF-AT(nuclear factor of activated T cell)‚ð’EƒŠƒ“Ž_‰»‚µŠj“à‚ֈڍs‚³‚¹‚éBŠj“à‚ֈڍs‚µ‚½NF-AT‚͐æq‚µ‚½AP-1‚Ɖ‚µIL-2‚Ȃǂ̃TƒCƒgƒJƒCƒ“ˆâ“`Žq‚Ì“]ŽÊ‚ð—U“±‚·‚éB



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@B×–E‚Å‚ÍT×–E‚Æ‘S‚­ˆÙ‚È‚éRŒ´”FŽ¯—lŽ®‚ð‚Æ‚é‚É‚à‚©‚©‚í‚炸A‚»‚Ì•¡‡‘̍\‘¢‚¨‚æ‚уVƒOƒiƒ‹“`’BŒn‚ª—ÞŽ—‚µ‚Ä‚¨‚èABCR/CD79•¡‡‘Ì‚ð‰î‚·‚é‘æ1ƒVƒOƒiƒ‹‚ƕ⏕ƒŒƒZƒvƒ^[‚ð‰î‚µ‚½‘æ2ƒVƒOƒiƒ‹‚ª‘¶Ý‚·‚éBBCR‚ªŽhŒƒ‚³‚ê‚é‚ÆLyn(Srcƒtƒ@ƒ~ƒŠ[PTK)‚ªŠˆ«‰»‚³‚êACD79‚ÌITAM‚ªƒ`ƒƒVƒ“ƒŠƒ“Ž_‰»‚ðŽó‚¯‚éBB×–E‚Å‚ÍT×–E‚ÌZAP-70‚Ì‘ã‚í‚è‚ÉSykƒLƒi[ƒ[‚ªITAM‚̃Šƒ“Ž_‰»ƒ`ƒƒVƒ“‚Ɖ‚µŠˆ«‰»‚ðŽó‚¯A‰º—¬‚ɃVƒOƒiƒ‹‚ð“`‚¦‚Ä‚¢‚­BBCRŽhŒƒ‚É‚æ‚éŽå‚ÈŒo˜H‚ÍT×–E‚ÌŽž‚Æ“¯—lAPLC‚ÌŠˆ«‰»‚É‚æ‚éCa2+Œo˜H‚¨‚æ‚ÑMAPKŒo˜HARac/JNKŒo˜H‹y‚ÑPI3KŒo˜H‚ª’m‚ç‚ê‚Ä‚¢‚éB

@ˆÈãAT×–E‚¨‚æ‚ÑB×–E‚ªRŒ´‚ð”FŽ¯‚µŽíX‚̈â“`Žq”­Œ»‚ÉŽŠ‚é‚Ü‚Å‚Ì—¬‚ê‚ɂ‚¢‚Ä‚»‚ÌŠT—ª‚ðq‚ׂ½BŽŸ‚ɁA–Ɖu“Ő«ì—p‚ðŽ¦‚·•¨Ž¿‚ª–ƉuŒn‚̃VƒOƒiƒ‹“`’BˆöŽq‚ɍì—p‚µ”j’]‚𐶂¶‚é‚Ü‚Å‚Ì‹@\‚ɂ‚¢‚āA–Ɖu“Ő«(—}§)•¨Ž¿‚Ü‚½‚͈öŽq‚Æ‚µ‚Ä’m‚ç‚ê‚Ä‚¢‚é‚à‚Ì‚ð‚¢‚­‚‚©—á‚É‚ ‚°‚Äà–¾‚µ‚½‚¢B

@Šˆ«Ž_‘f‚́AŠOŠE‚©‚ç×‹Û‚ªN“ü‚·‚é‚ƍD’†‹…‚âƒ}ƒNƒƒtƒ@[ƒW‚Ȃǂ̍זE‚©‚çŽY¶‚³‚ê‚éB‚±‚ÌŠˆ«Ž_‘f‚ÍŽE‹Ûì—p‚ðŽ¦‚µ¶‘̖̂ƉuƒVƒXƒeƒ€‚ÉŠÖ—^‚µ‚Ä‚¢‚邪A‰ß“x‚É•úo‚³‚ê‚é‚ÆŒŒŠÇŠg’£‚⌌ŠÇ“§‰ß«‚ª˜´i‚µ‰ŠÇ‚ªˆø‚«‹N‚±‚³‚ê‘gDŠQ“I‚É“­‚­B‚±‚̂悤‚ɍRŽ_‰»–hŒäƒVƒXƒeƒ€‚ª‚¤‚Ü‚­“­‚©‚¸‚É‹N‚«‚銈«Ž_‘f‚É‚æ‚éŠQ‚ÍŽ_‰»ƒXƒgƒŒƒX‚ƌĂ΂ê‚éBŽ_‰»ƒXƒgƒŒƒX‚̓Šƒ“ƒp‹…‚É‚¨‚¢‚āAPLC‚ÌŠˆ«‰»‚ð‰î‚µ‚ĉº—¬‰ž“š‚ð—U“±‚·‚éZAP-70‚ðƒŒƒZƒvƒ^[”ñˆË‘¶“I‚ÉŠˆ«‰»‚·‚邱‚Æ‚ÅPTKˆË‘¶«ƒVƒOƒiƒ‹‚̐§Œä‚ð”j‰ó‚·‚é5)BPLC‚ÌŠˆ«‰»‚É‚æ‚è×–E“àCa2+”Z“x‚ªã¸‚µACa2+’²ß•s‘S‚ðˆø‚«‹N‚±‚·B‚Ü‚½‘æ1ƒVƒOƒiƒ‹‚ðŒ¸Žã‚³‚¹AƒAƒ|ƒg[ƒVƒX‚ð—U“±‚·‚éBŽ_‰»ƒXƒgƒŒƒX‚ƒʏí‚Ì‘æ1ƒVƒOƒiƒ‹‚ÍPLC‚ÌŠˆ«‰»‚ÉŠÖ˜A‚·‚鋤’Ê‚ÌPTK‚ðŠˆ«‰»‚·‚邪A‚»‚ê‚ç‚͈قȂ郁ƒJƒjƒYƒ€‚ð‰î‚µ‚½Œo˜H‚ŃVƒOƒiƒ‹‚ð“`’B‚·‚éB‘½ŠÂ–F‘°’Y‰»…‘f(PAHs)‚àPTK‚ÌŠˆ«‰»‚ðƒŒƒZƒvƒ^[”ñˆË‘¶“I‚É—U“±‚·‚éB‚³‚ç‚ɏ¬–E‘Ì–Œó‚ÌCa2+-ATPaseƒ|ƒ“ƒv(sarcoplasmic/ endoplasmic reticulum Ca2+-ATPase; SERCA)‚ð‘jŠQ‚·‚邱‚Æ‚ÅCa2+‚̏¬–E‘̂ւ̍Ďæ‚荞‚Ý‚ð‘jŠQ‚µA×–E“àCa2+”Z“x‚ðã¸‚³‚¹‚éB‚Ü‚½Ž_‰»ƒXƒgƒŒƒX‚É‚æ‚Á‚ÄHO-1(heme oxygenase-1)‚ÌŽY¶‚à—U“±‚³‚ê‚é6,7)BHO-1‚̓wƒ€‚ð•ª‰ð‚·‚éy‘f‚Å‚ ‚èAŠÌ‘Ÿ‚âäB‘Ÿ‚ō‚ƒŒƒxƒ‹‚É”­Œ»‚µ‚Ä‚¢‚éBHO-1‚ÍLPSŽhŒƒ‚É‚æ‚Á‚Ä‚à—U“±‚³‚êA‚»‚̍ۉŠÇ«ƒTƒCƒgƒJƒCƒ“‚Å‚ ‚éIL-1ƒ¿/ƒÀ‚âˆêŽ_‰»’‚‘fATNF-ƒ¿‚ªŠÖ—^‚µ‚Ä‚¢‚é‚Æ‚Ì•ñ‚ª‚ ‚éBHO-1ˆâ“`Žq‚ÍJNK‚È‚Ç‚ÌŒo˜H‚ð‰î‚µ‚ÄAP-1‚ªŠˆ«‚³‚ê‚邱‚Æ‚Å”­Œ»‚³‚ê‚éB

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ѻΐ
AP-1:activator protein-1
CN:calcineurin
DAG:diacylglycerol
IP3:inositol 1,4,5-trisphosphate
ITAM:immunoreceptor tyrosine-based activation motif
JNK: c-Jun N-terminal kinase
LAT:linker for activation of T cell
MAPK:mitogen-activated protein kinase
MHC:major histocompatibility complex
NF-AT: nuclear factor of activated T cell
PI3K: phosphatidyl inositol 3-kinase
PIP3: phosphatidyl inositol 3,4,5-trisphosphate
PKC: protein kinase C
PLC: phospholipase C
PTK: protein tyrosine kinase
SLP-76: SH2 domain-containing leukocyte protein of 76 kD
TCR: T cell receptor
ZAP-70: Zeta-associated protein-70