Iaoe?iiaeueia aeaaeai?y iaoe Oe?a?ie
?inoeooo aenia?eiaioaeueii? iaoieia??, iieieia?? ? ?aae?ia?ieia??
?i. ?.?.Eaaaoeueeiai
I?i?noa?noai ioi?iie caei?ia’y Oe?a?ie
Oe?a?inueeee iaoeiai-aeine?aeiee ?inoeooo iieieia?? oa ?aae?ieia??
OIAOA AIAe??E ?AAIIAE*
OAeE 616-006.6:57.052.6+.042.2
NAE?AOe?ss EOEUeOEAIAAIEIE EE?OEIAIE AI?AeA?II?AeII? EA?OeEIIIE IAIOEAeO
C AEANOEAINOssIE ?IA?A?OI?A I?IOA?IE?IAC
14.01.07 – iieieia?y
AAOI?AOA?AO
aeena?oaoe?? ia caeiaoooy iaoeiaiai nooiaiy
eaiaeeaeaoa a?ieia?/ieo iaoe
Ee?a – 1999
Aeena?oaoe??th ? ?oeiien.
?iaioa aeeiiaia a ?inoeooo? aenia?eiaioaeueii? iaoieia??, iieieia?? ?
?aae?ia?ieia?? ?i. ?.?.Eaaaoeueeiai IAI Oe?a?ie
Iaoeiaee ea??aiee – – eaiaeeaeao a?ieia?/ieo iaoe Iia??aiee Iao?i
Aaneeueiae/,
noa?oee iaoeiaee ni?a?ia?oiee a?aeae?eo a?ieia?? iooeeiii? ee?oeie
?inoeoooo aenia?eiaioaeueii? iaoieia??, iieieia?? ? ?aae?ia?ieia?? ?i.
?.?.Eaaaoeueeiai IAI Oe?a?ie.
Io?oe?ei? iiiiaioe :
– aeieoi? a?ieia?/ieo iaoe Eacuei?i Na?a?e Aeieo?iae/, i?ia?aeiee
iaoeiaee ni?a?ia?oiee a?aeae?eo a?io?i?? iooeei ?inoeoooo
aenia?eiaioaeueii? iaoieia??, iieieia?? ? ?aae?ia?ieia?? ?i.
?.?.Eaaaoeueeiai IAI Oe?a?ie.
– aeieoi? a?ieia?/ieo iaoe Aa?aaiaoeue Ethaeieea Aeieo??aia, caa?aeoaa/
a?aeae?eo a?io?i?? i?e?ii?aai?ci?a ?inoeoooo i?e?ia?ieia?? oa
a??onieia?? ?i. Ae.E.Caaieioiiai IAI Oe?a?ie.
I?ia?aeia onoaiiaa-
Ee?anueea iaaee/ia aeaaeai?y i?neyaeeieiiii? ina?oe ?i. I.E.Ooieea IIC
Oe?a?ie, eaoaae?a iieieia??
Caoeno a?aeaoaeaoueny “26”_o?aaiy______1999 ?. i _16:00
ia can?aeaii? niaoe?ae?ciaaii? a/aii? ?aaee Ae.26.155.01 a ?inoeooo?
aenia?eiaioaeueii? iaoieia??, iieieia?? ? ?aae?ia?ieia?? ?i.
?.?.Eaaaoeueeiai IAI Oe?a?ie (252022, i. Ee?a, aoe. Aaneeuee?anueea,
45).
C aeena?oaoe??th iiaeia iciaeiieoenue a a?ae?ioaoe? ?AII? ?i.
?.?.Eaaaoeueeiai
Aaoi?aoa?ao ?ic?neaiee “_23_”___ea?oiy_________ 1999 ?.
A/aiee nae?aoa? niaoe?ae?ciaaii? a/aii? ?aaee
aeieoi? iaaee/ieo iaoe
?.A.Aa?aiaiei
CAAAEUeIA OA?AEOA?ENOEEA ?IAIOE
Aeooaeuei?noue oaie.
Iieiaaiac noi?iaiaeaeo?oueny aeenaaeainii a i?iaeoeoe?? ee?oeiaie
oaeoi??a ?inoo ? ?o ?aoeaioi??a. Iooeeii? ee?oeie i?iaeoeothoue
iie?iaioeaei? oaeoi?e ?inoo, ui caaacia/oth? a cia/i?e i??? aaoiiiiiee
??no iiaiooai?aiue (Rudland et al., 1998, Smits, Funa, 1998), a oaeiae
caeaoi? aei nae?aoe?? oaeoi??a, ui i?eai?/othoue i?ie?oa?aoe?th ee?oei
(Bogdahn et al., 1989).
C?o/iith aenia?eiaioaeueiith iiaeaeeth aeey aea/aiiy nae?aoe?? oaeoi??a
iaio a?oi ? eoeueoeaiaai? iooeeii? ee?oeie ??cieo e?i?e. O ca’yceo c
oeei ?c canoinoaaiiyi iaoiae?a aaiii? ?iaeaia??? neiino?oeiaaii ?yae
ee?oeiieo noae?i?e, ui aiaeii/an a?ia?aeni?anothoue ?aeiia?iaioiee
o?ainoi?ioth/ee oaeoi? ?inoo a (OO?a) ? ?aoeaioi? ai?aea?iaeueiiai
oaeoi?a ?inoo (McGeady et al., 1989, Iia?aaiie n niaao., 1993, 1997).
Ee?oeie aeaieo noae?i?e oa?aeoa?ecothoueny a?eueo ceiye?niei oaiioeiii,
i?ae ?o iiia?aaeieee, ca ?aooiie i?oiaaiii? ae?? OO?a, ui, ye ?
ai?aea?iaeueiee oaeoi? ?inoo (AO?), ? e?aaiaeii ?aoeaioi?a AO?.
Iaioeaee, nae?aoiaai? iooeeiieie ee?oeiaie, iiaeooue aieeaaoe ia
noi?aei? ee?oeie /a?ac ae?th ia iao?een ieaciaoe/ii? iaia?aie,
i?ioaiae?eaie ee?oeiii? iaieiiee, iaia?aii? a?eee ? eiiiiiaioe
oeeoineaeaoo (He et al., 1998, Iia?aaiie n niaao., 1997). Oiio
aeine?aeaeaiiy niaeo?o ?o a?ieia?/ii? aeoeaiino?, iaoai?ci?a ae?? ? oiia
i?iaeoeoe?? ? aeooaeueiith caaea/ath no/anii? iieieia??.
Ca’ycie ?iaioe c iaoeiaeie i?ia?aiaie, ieaiaie, oaiaie.
Aeena?oaoe?eia ?iaioa aeeiiaia o a?aeae?e? a?ieia?? iooeeiii? ee?oeie
?inoeoooo aenia?eiaioaeueii? iaoieia??, iieieia?? ? ?aae?ia?ieia?? ?i.
?.?.Eaaaoeueeiai IAI Oe?a?ie ca?aeii c ieaiii iaoeiai-aeine?aeii? ?iaioe
ca oaiith: 0198U001092 “Aeine?aeaeaiiy o/ano? aeaoaineiiiae?aieo
iaioeae?a a ?aae?caoe?? iooeeiiiai oaiioeio ee?oei oa aecia/aiiy
iiaeeeainoae ?o aeei?enoaiiy a iieieia?/i?e ee?i?oe?”. ?iaioa
aeeiioaaeanue ca i?aeo?eiee a?aioaie I?i?noa?noaa Oe?a?ie a ni?aaao
iaoee ? oaoiieia?e (i?iaeo: 2/1297-97 “?ic?iaea oaoiieia?? io?eiaiiy oa
canoinoaaiiy oaiie?i?a oa oeae?ii?i?a ye i?ioeiooeeiieo cania?a”) ?
Aea?aeaaiiai oiiaeo ooiaeaiaioaeueieo aeine?aeaeaiue (i?iaeoe: 5.2/80
“Aea/aiiy ?aaoeyoi?ieo iaoai?ci?a i?ie?oa?aoe?? ee?oei, ye? aooie?eiii
i?iaeoeothoue o?ainoi?ioth/ee oaeoi? ?inoo aeueoa” ? 5.4/388 “Iaioeaee
oeae?ii?iiaiai ?yaeo ye aioea?ioeee ? iiaeeea? /eiieee ianiaoeeo?/iiai
?ioi?oaoo i?e ceiye?ni?e o?ainoi?iaoe?? ee?oei.”). Oeo? i?iaeaie
2.29.1.3.
Iaoa ? caaea/? aeine?aeaeaiiy.
Iaoa ?iaioe – aeae?eeoe iaioeaei? oaeoi?e, ui nae?aoothoueny
eoeueoeaiaaieie iooeeiieie ee?oeiaie ? i?eeiathoue o/anoue a ?aaoeyoe??
?inoo ee?oei oeyoii aieeao ia aeoeai?noue i?ioa?ie?iac, a oaeiae
ioa?aeoa?ecoaaoe ?o a?ieia?/io ae?th in vitro.
Iniiai? caaea/? aeine?aeaeaiiy:
– ne?eieia na?aaeiaeu ?ieoaaoe?? ee?oei ia iayai?noue eiiiiiaio?a,
caeaoieo aieeaaoe ia oinoi?eethaaiiy ?aoeaioi?a AO?;
– ?ic?iaea noaie aeae?eaiiy iaioeaeo c aeanoeainoyie ?ia?a?oi?a
i?ioa?ie?iac;
– aecia/aiiy aioei?e?iaii? aeoeaiino? aeae?eaiiai iaioeaeo;
– oa?aeoa?enoeea ae?? iaioeaeo ia i?ioa?ie?iace, aeae?eai? c ee?oei, ?
aeea? ee?oeie in vitro;
– aecia/aiiy oiia nae?aoe?? iaioeaeo c aeanoeainoyie ?ia?a?oi?a
i?ioa?ie?iac eoeueoeaiaaieie iooeeiieie ee?oeiaie.
Iaoeiaa iiaecia iaea?aeaieo ?acoeueoao?a.
A oiae? i?iaaaeaieo aenia?eiaio?a a io?eiaieo ca aeiiiiiaith iaoiae?a
aaiaoe/ii? ?iaeaia??? ee?oeiao, ui aiaeii/an a?ia?aeni?anothoue
?aoeaioi? AO? ? caeaoi? i?iaeoeoaaoe eiai e?aaiae (a aeaiiio aeiaaeeo
?aeiia?iaioiee OO?a), aia?oa aeyaeaii nae?aoe?th iaioeaeo, yeee ia?
aeanoeaino? ?ia?a?oi?a i?ioa?ie?iac, a oaeiae i?iyaey? aaeoa?eoeeaeio ?
aaiie?oe/io aeoeai?noue. Iaioeae aeae?eaii ? ioa?aeoa?eciaaii niaeo?
eiai a?ieia?/ii? ae??. Aeey aeae?eaiiai iaioeaeo cai?iiiiiaaii iacao
AIAE.
Iniaenoee aianie caeiaoaa/a.
Iniiai? ?aea?, iaoeia? iieiaeaiiy ? aeniiaee ?ic?iaeai? ? ioi?ieai?
aeena?oaioii naiino?eii. Aeena?oaio aaciina?aaeiuei i?aoethaaa c
eoeueoo?aie ee?oei, aoa caae?yiee ia an?o aoaiao aeae?eaiiy
aioei?e?iaiiai iaioeaeo c aeanoeainoyie ?ia?a?oi?a i?ioa?ie?iac, a
oaeiae o aea/aii? eiai a?ieia?/ieo aeanoeainoae. Aeena?oaioii naiino?eii
i?iaaaeai? aeine?aeaeaiiy aaiie?oe/ii? ? aaeoa?eoeeaeii? aeoeaiino?
iaioeaeo. A i?ioean? aeeiiaiiy aeena?oaoe?? aaoi? iniaenoi a?ae?a?aa oa
e?eoe/ii i?iaiae?coaaa aeinooiio e?oa?aoo?o, yea ia? a?aeiioaiiy aei
oaie aeine?aeaeaiiy.
Ai?iaaoe?y ?acoeueoao?a aeena?oaoe??.
Iniiai? ?acoeueoaoe ? iieiaeaiiy aeena?oaoe?? aoee ai?iaiaai? ia 8-io
?a?iiaenueeiio eiia?an? c a?ioaoiieia?? (Aoaeaiaoo, Oai?ueia, 1997) ? ia
I?aeia?iaeieo eo?nao FEBS “Iieaeoey?i? iaoai?cie aaeoa??aeueii?
?ioaeoe??” (Niaoean, A?aoe?y, 1998).
Ioae?eaoe??.
Ca iaoa??aeaie aeena?oaoe?? iioae?eiaaii 5 iaoeiaeo noaoae a i?ia?aeieo
oaoiaeo aeaeaiiyo.
No?oeoo?a ? ianya aeena?oaoe??.
Aeena?oaoe?y aeeeaaeaia ia 139 noi??ieao ae?oeiaaiiai oaenoo,
neeaaea?oueny ?c anooio, iaeyaeo e?oa?aoo?e, ?icae?eo c iienii
iaoa??ae?a ? iaoiae?a aeine?aeaeaiue, 5 ?icae?e?a, i?enay/aieo iieno
aeanieo aeine?aeaeaiue, a oaeiae aiae?co ? ocaaaeueiaiith ?o
?acoeueoao?a, aeniiae?a ? nieneo aeei?enoaieo e?oa?aoo?ieo aeaea?ae (207
iaeiaioaaiue, c ieo oe?a?inueeith oa ?in?enueeith iiaaie – 19,
?iicaiieie iiaaie – 188). Aeena?oaoe?y ?ethno?iaaia 21 ?enoieii, 2
oaaeeoeyie.
CI?NO ?IAIOE
?icae?e 1. Iaeyae e?oa?aoo?e.
Iaoa??ae ?icae?eo a?aeia?aaea? no/aniee noai ciaiue i?i o?ainoi?ioth/ee
oaeoi? ?inoo a, ?aoeaioi? ai?aea?iaeueiiai oaeoi?a ?inoo, ?o
i?iaeoeoe?th ? o?c?ieia?/io ?ieue. Ei?ioei ioa?aeoa?eciaai? ee?oeii?
noae?i?? A431/1522 ? I-IeLa/1522, ui i?iaeoeothoue ?aeiia?iaioiee OO?a.
I?eaaaeaii iaeyae a?aeiieo iaioeae?a oaa?eiiiai iioiaeaeaiiy, ye?
iathoue aioei?e?iaio aeoeai?noue.
?icae?e 2. Iaoa??aee ? iaoiaee aeine?aeaeaiue.
Nae?aoe?th iaioeae?a eoeueoeaiaaieie ee?oeiaie noae?i?? A431/1522
?iaeoeoaaee noeioeyoe??th aeni?an?? ?aeiia?iaioiiai OO?a. Aeey oeueiai
ee?oeie, ui aeinyaee noaeiioethaioo, ?ieoaoaaee a na?aaeiaeu? aac
ne?iaaoee, ui i?noeei 3 ieI CdCl2, i?ioyaii 2 ae?a, ye iienaii
I.A.Iia??aiei c ni?aaao. (1993, 1997). ?ia?a?oi?io aeoeai?noue
i?aia?ao?a na?aaeiaeu ?ieoaaoe?? ii a?aeiioaiith aei i?ioa?ie?iace
?aoeaioi?a AO? aeine?aeaeoaaee o ?aaeoe?? aooioinoi?eethaaiiy in vitro a
i?aia?aoao ieaciaoe/ieo iaia?ai ee?oei e?i?? A431. Ieaciaoe/i? iaia?aie
io?eioaaee o aeaeyae? aaceeoe ca iaoiaeeeith, cai?iiiiiaaiith Payrastre
et al. (1991). Oinoi?eethaaiiy ?aoeaioi?a AO? i?iaiaeeee c o?aooaaiiyi
i?ioieieo TH.Ae.?aauaiea c ni?aaao. (1989). Eiaaeaioia i?/aiiy
?aoeaioi?a AO? i?aia?aoii 125?-AO? i?iaiaeeee ca aeiiiiiaith
noeoeei?i?aeeenoaa?aoo ca?aeii ?aeiiaiaeaoe?e TH.Ae.?aauaiea c ni?aaao.
(1986).
Aeey aeae?eaiiy AIAE aoei canoiniaaii eiia?iaoe?th o?iiaoia?ao?/ieo
i?ioeaaeo?, a yeeo e?eoa???i a?aeai?o o?aeoe?e aoea aaeoa?eoeeaeia
aeoeai?noue ii a?aeiioaiith aei Bacillus mesentericus ATCC 31029.
Na?aaeiaeua ?ieoaaoe?? ee?oei o?eueo?oaaee, e?io?e?coaaee, ia?a?ic/eiyee
a aea?ii?ciaai?e aiae?, aeiaiaeeee pH aei 4,0 ioeoiaith eeneioith ?
oeaio?eooaoaaee i?e 10000 g i?ioyaii 10 oaeeei. Aeey ca?eueiaiiy a?ae
aenieiiieaeoey?ieo eiiiiiaio?a ? /anoeiaiai iaacnieaiiy noia?iaoaioe
iaiineee ia eieiieo PD-10 (Pharmacia, Oaaoe?y). Aethaoe eiioeaio?oaaee
ca aeiiiiiaith i?i?-eieiiie Sep-Pak C18 (Waters, NOA). Aethoe?th
i?iaiaeeee nooi?i/anoei a?aae??ioii aoeaoii?o?eeo (10% ? 70%, aai 10%,
40% ? 70%). A?ae?a?ai? o?aeoe?? ?icae?eyee aaeue-o?eueo?aoe??th aenieiai
oeneo ia eieiioe? OSK-GEL Toyopearl HW-40 (Toyo-Soda, ssiii?y). A yeino?
o?iaeueiiai aoaio i/enoee AIAE canoiniaoaaee ??aeeiio o?iiaoia?ao?th
aenieiai oeneo a iaa?iai?e oac? ia eieiioe? Pep-RPC 5/5 C2-C18
(Pharmacia, Oaaoe?y). Eiioeaio?aoe?th AIAE ia?aoiaoaaee ca ieiuath i?eo.
Io?eiaiee i?aia?ao AIAE ?ao?iiaoia?aooaaee ia eieiioe? Ultrasphere ODS
5m (Beckman, NOA), i?ney /iai eiai aiiiaaii?noue ia?aa??yee
aeaeo?ioi?acii a ?aaeoeoth/eo oiiaao a nenoai? aooa??a Laemmli (1970).
Aioei?e?iaio aeoeai?noue AIAE aecia/aee ca i?eai?/aiiyi ?inoo aaeoa??e a
oiieiio oa?? aaa?ice iaoiaeii Hultmark et al. (1983) c iacia/ieie
iiaeeo?eaoe?yie.
?ia?a?oi?io aeoeai?noue AIAE ii a?aeiioaiith aei i?ioa?ie?iac aecia/aee
o ?aaeoe?? oinoi?eethaaiiy in vitro. A yeino? aeaea?aea ?aoeaioi?a AO?
aeei?enoiaoaaee i?aia?aoe ieaciaoe/ieo iaia?ai ee?oei e?i?? A431.
Aeoeai? oeeoicieuei? i?ioa?ie?iace (Lyn, Syk, PKCm) aoee io?eiai? i?e
o/ano? e.a.i. N.A.I?oaeai, e.a.i. E.I.Oeaiaoeueei?, e.a.i. A.A.Aa?aeiai?
? ae.a.i. N.I.Neaei?aiei ?ioiii?aoeei?oaoe??th iiiieeiiaeueieie
aioeo?eaie c e?cao?a ee?oei e?i?? CESS. A yeino? eiio?iey
aeei?enoiaoaaee aioeo?ea Mab MOPC (an? aioeo?ea o??ie Santa Cruz
Biotech, NOA). Aeaineoiiao??th ?aae?iaaoia?ao?a ? ia/eneaiiy
?acoeueoao?a i?iaiaeeee i?e o/ano? N.?.?iiaithe ? Ae.A.Eieeai ca
aeiiiiiaith i?ia?aie “Densitometry” (aaoi? A.A.Aiae, OaiiOaeaeii,
Oe?a?ia).
I?eai?/aiiy neioaco AeIE a ee?oeiao e?i?e Namalwa ? Jurkat ioe?ithaaee
ca ?iei?ii?aoe??th 3I-oei?aeeio (Oannaiia, 1979) i?e ?ieoaaoe?? a
i?enooiino? ??cieo eiioeaio?aoe?e AIAE. AEeoo?caeaoi?noue ee?oei a
eoeueoo?ao aecia/aee ca caaa?aeaiiyi 0,2%-i ?ic/eiii o?eiaiiaiai
neiueiai.
Aaiie?oe/io aeoeai?noue AIAE aeaoaeooaaee ca e?cenii a?eo?ioeeo?a
ethaeeie a oiieiio oa?? aaa?ice. AIAE a na??eieo ?icaaaeaiiyo aiineee a
eoiee, i?iaeo? a aaa?ic?. I?i?iaeueio aaiie?oe/io eiioeaio?aoe?th
aecia/aee aeno?aiieyoe??th caeaaeiino? ieiu? ciie aaiie?co a?ae
eiaa?eoio eiioeaio?aoe?? AIAE ia cia/aiiy ieiu? eoiee.
Oeeo?iaee iaoa??ae, i?aaenoaaeaiee o aeena?oaoe?ei?e ?iaio?, i?aeeyaaa
aa??aoe?eii-noaoenoe/i?e ia?iaoe? (O?aao, 1975).
?icae?e 3. Aooinoeioeyoe?y ee?oei aiaeiaaiiei OO?a ?iaeoeo? nae?aoe?th
?ia?a?oi?a aooioinoi?eethaaiiy ?aoeaioi?a AO?.
I?e aeine?aeaeaii? aieeao i?aia?ao?a, io?eiaieo c na?aaeiaeu ?ieoaaoe??
iooeeiieo ee?oei ??cieo e?i?e, ia aeoeai?noue e?iace ?aoeaioi?a AO? aoei
iieacaii, ui aeaye? c ieo caeaoi? i?eai?/oaaoe ye oiiiaa, oae ?
AO?-caeaaeia aooioinoi?eethaaiiy ?aoeaioi?a AO?. Iaea?eueo ae?aaeaiee
?ia?a?oi?iee aieea ia i?ioa?ie?iacio aeoeai?noue ?aoeaioi?a AO?
cae?eniththoue i?aia?aoe na?aaeiaeu ?ieoaaoe?? ee?oei noae?i??
A431/1522, ye? aoee ?iaeoeiaai? aei aeni?an?? eAeIE OO?a.
Aeey iiyniaiiy yaeua, ui niinoa??aa?oueny, aoei ai?iaaaeaeaii
o?aeoe?thaaiiy iaioeae?a c na?aaeiaeua ?ieoaaoe?? ee?oei noae?i??
A431/1522 nooi?i/anoei a?aae??ioii aoeaoii?o?eeo (10%, 40% ? 70%) ca
aeiiiiiaith i?i?-eieiiie Sep-Pak C18. O?aeoe??, aetheiaai? 40% (aeae? –
“O1”) ? 70% (aeae? – “O2”) aoeaoii?o?eeo, oanooaaee ia AO?-eiieo?aioio
aeoeai?noue ? caeaoi?noue cae?enithaaoe aieea ia aooioinoi?eethaaiiy
?aoeaioi?a AO? a i?aia?aoao ieaciaoe/ieo iaia?ai ee?oei e?i?? A431.
Aeey aeine?aeaeaiiy AO?-eiieo?aioii? aeoeaiino? o?aeoe?e aoei
canoiniaaii eiieo?aioiee aa??aio eiaaeaioiiai i?/aiiy ?aoeaioi?a AO?
i?aia?aoii 125?-AO?. ?aae?iaaoia?ao, iaaaaeaiee ia ?en. 1, aeaiiino?o?
AO?-eiieo?aioio aeoeai?noue o?aeoe?? O1, ui iiynith?oueny i?enooi?noth a
i?e ?aeiia?iaioiiai OO?a, ? ?? a?aenooi?noue o o?aeoe?? O2.
Aieea o?aeoe?e ia ?ioaineai?noue aooioinoi?eethaaiiy ?aoeaioi?a AO?
i?aaenoaaeaii ia ?en. 2. O?aeoe?y, aetheiaaia 40% aoeaoii?o?eeo (O1),
caaaeyee ae?? OO?a, noeioeth? aooioinoi?eethaaiiy ?aoeaioi?a AO? in
vitro. Aeiaeaaaiiy ae eiiiiiaio?a o?aeoe??, aetheiaaii? 70%
aoeaoii?o?eeo (O2), a aiaeia?/ieo oiiaao i?ecaiaeeoue aei cieaeaiiy
??aiy oinoi?eethaaiiy ?aoeaioi?a AO?.
Noaey/e c iaaaaeaieo ?acoeueoao?a, i?eai?/aiiy aooioinoi?eethaaiiy
?aoeaioi?a AO? eiiiiiaioaie na?aaeiaeu ?ieoaaoe?? ee?oei ne?ae a?aeianoe
ia ?aooiie i?yiiai ?ia?aoaaiiy e?iace ?aoeaioi?a, a ia eiieo?aioe?? c
e?aaiaeaie ca naeoe ca’ycoaaiiy.
?enoiie 1. ?aae?iaaoia?ao eiaaeaioiiai i?/aiiy ?aoeaioi?a AO? i?aia?aoii
125?-AO?: 1 – a i?enooiino? iaaeeeoeo AO?; 2, 3 – a i?enooiino? a?ee?a
na?aaeiaeua ?ieoaaoe?? ee?oei noae?i?? A431/1522 (2 – O1; 3 – O2); 4 –
eiio?ieue.
?enoiie 2. ?aae?iaaoia?ao oinoi?eethaaiiy a i?aia?aoao iaia?ai ee?oei
e?i?? A431: 1 – eiio?ieue; 2-4 – i?e aeiaeaaaii? iaioeaeieo o?aeoe?e
na?aaeiaeua ?ieoaaoe?? ee?oei noae?i?? A431/1522, aetheiaaieo
a?aeiia?aeii 10%, 40% ? 70% aoeaoii?o?eeo; 5 – a i?enoioino? 0,1 ieI
AO?.
?acoeueoaoe aooioinoi?eethaaiiy ?aoeaioi?a AO? i?e aeei?enoaii?
ianietha?e?ciaaieo iaia?aiieo aaceeoe iieacaee, ui aieea o?aeoe?? O2 ia
oinoi?eethaaiiy a i?iaao iiae?aiee aei ae?? iae?oeio, oieneia yaeo
iaaeiiinii? aaeaeiee, ui caeaoiee ooai?thaaoe ii?e a e?i?aeieo
iaia?aiao. Oea na?ae/eoue ia ei?enoue a?iioace i?i caeaoi?noue
eiiiiiaio?a o?aeoe?? O2 aei aca?iiae?? c iaia?aiaie ? ?o
ia?iaaa?e?caoe??.
?icae?e 4. Aeae?eaiiy iaioeaeo c aeanoeainoyie ?ia?a?oi?a i?ioa?ie?iac
(AIAE) ?c na?aaeiaeua ?ieoaaoe?? ee?oei noae?i?? A431/1522.
Ia iniia? aiae?co ?acoeueoao?a aeanieo aeine?aeaeaiue ? ni?anoaaeaiiy ?o
c aeaieie e?oa?aoo?e aoei aenoiooa i?eiouaiiy i?i iioaioe?eio
nii??aeiai?noue iaioeaeiiai ?ia?a?oi?a i?ioa?ie?iace ?aoeaioi?a AO?, ui
nae?aoo?oueny eoeueoeaiaaieie ee?oeiaie, c aeaoaineiaie – aioei?e?iaieie
iaioeaeaie, ui i?iaeoeothoueny oaaioeeoaie ? ee?oeiaie iie?eaieo oeaiei
nnaaoe?a. C oeeo i??eoaaiue aoei canoiniaaii oanooaaiiy i?aia?ao?a,
io?eiaieo ?c na?aaeiaeu ?ieoaaoe?? ee?oei, ia caeaoi?noue i?eai?/oaaoe
??no aaeoa??e a oiieiio oa?? aaa?ice. I?e oeueiio aoei aeyaeaii i?yio
ei?aeyoe?th aioei?e?iaii? aeoeaiino? i?aia?ao?a c ?o caeaoi?noth
i?eai?/oaaoe i?ioa?ie?iacio aeoeai?noue ?aoeaioi?a AO?. Iaaeae?
oanooaaiiy aioei?e?iaii? aeoeaiino? o?aeoe?e aoei canoiniaaii ia an?o
aoaiao i/enoee iaioeaeo.
?enoiie 3. I?io?eue aethoe?? eiiiiiaio?a na?aaeiaeua ?ieoaaoe?? ee?oei
noae?i?? A431/1522 i?e aaeue-o?eueo?aoe?? aenieiai oeneo. No??eeaie
a?aei?/aii /an aethoe?? ia?ea??a iieaeoey?ii? iane (12 eAe – oeeoio?ii
N, 6 eAe – ?inoe?i, 3 eAe – iae?oei).
A?aoiaoth/e ?iaioe ii i/enooe? aioei?e?iaieo iaioeae?a oaa?ei (Moore et
al., 1991, Fehlbaum et al., 1996 oa ?i.), aeey aeae?eaiiy iaioeaeo c
aeanoeainoyie ?ia?a?oi?a i?ioa?ie?iac c na?aaeiaeu ?ieoaaoe?? ee?oei
noae?i?e A431/1522 aoea canoiniaaia ianooiia iine?aeiai?noue
o?iiaoia?ao?/ieo i?ioeaaeo?: aaeue-o?eueo?aoe?y iecueeiai oeneo,
eiioeaio?aoe?y ia i?i?-eieiieao Sep-Pak C18, aaeue-o?eueo?aoe?y aenieiai
oeneo, ??aeeiia o?iiaoia?ao?y aenieiai oeneo a iaa?iai?e oac? (IO ?OAO)
c ianooiiith ?ao?iiaoia?ao??th. A ?acoeueoao? IO ?OAO o?aeoe?y, ui ia?
aioei?e?iaio aeoeai?noue, aeeoea ?aeeiei neiao?e/iei i?eii a 62%
aoeaoii?o?eeo. Caeeth/i? aoaie io?eiaiiy AIAE i?i?ethno?iaaii
o?iiaoia?aiaie (?en. 3, 4). Nooi?iue aiiiaaiiino? i?aia?aoo ioe?ithaaee
aeaeo?ioi?acii.
I?e aeei?enoaii? cai?iiiiiaaii? noaie c 100 ie na?aaeiaeua aaea?oueny
aeae?eeoe a na?aaeiueiio aeecueei 5 iea iaioeaeo. Aeey io?eiaiiai
i?aia?aoo aoei cai?iiiiiaaii iacao AIAE (nei?i/aii a?ae: aioei?e?iaiee
iaioeae c ee?oei ai?aea?ii?aeii? ea?oeeiiie) (Pogrebnoy et al., 1998).
?enoiie 4. I?io?eue aethoe?? i?e i/enooe? AIAE ca aeiiiiiaith IO ?OAO ia
eieiioe? Pep-RPC 5/5 C2-C18. No??eeith aeacaiee /an aethoe?? AIAE.
Iieaeoey?ia iana AIAE, aecia/aia aaeue-o?eueo?aoe??th, noaiiaeoue
aeecueei 5 eAe. I?e aeaeo?ioi?ac? a ?aaeoeoth/eo oiiaao AIAE
aecia/a?oueny iaei??th nioaith. Eiai aeaeo?ioi?aoe/ia ?ooii?noue
a?aeiia?aea? iieaeoey?i?e ian? aeecueei 3 eAe ? caeaaeeoue a?ae oiia
i?iaaaeaiiy aeaeo?ioi?aco. Iaa?aeiia?aei?noue o aecia/aieo cia/aiiyo
iieaeoey?ii? iane, ?iia??ii, iiynith?oueny caeaoi?noth iaioeaeo aei
aeeia?ecaoe?? a ?ic/ei?, ye oea iieacaii aeey aeaoainei?a (Hill et al.,
1991).
?icae?e 5. Oa?aeoa?enoeea a?ieia?/ii? aeoeaiino? AIAE.
A yeino? e?eoa???a a?ieia?/ii? aeoeaiino? io?eiaiiai i?aia?aoo AIAE
aeine?aeaeoaaee eiai ae?th ia aaeoa???, eoeueoeaiaai? ee?oeie ?
a?eo?ioeeoe ethaeeie a noniaic??, a oaeiae aieea ia aeoeai?noue
i?ioa?ie?iac, aeae?eaieo c ee?oei.
?enoiie 5. Aecia/aiiy i?i?iaeueii? ?ia?a?oi?ii? eiioeaio?aoe?? AIAE ii
a?aeiioaiith aei Bacillus mesentericus ? Pseudomonas aeruginosa.
Caeaaei?noue ieiu? ciie, a?eueii? a?ae aaeoa??aeueiiai ?inoo, a?ae
eiaa?eoio eiioeaio?aoe?? AIAE.
Aeey aecia/aiiy aioei?e?iaii? aeoeaiino? AIAE eiai aiineee a eoiee,
i?iaeo? a oa?? aaa?ice, can?yii? oano-eoeueoo?aie. Cia/aiiy i?i?iaeueii?
?i?a?a?oi?ii? eiioeaio?aoe?? (IC) aecia/aeinue ?c caeaaeiino? ieiu?
ciie, a?eueii? a?ae i?e?iaiiai ?inoo, a?ae eiaa?eoio eiioeaio?aoe?? AIAE
a i?ia? aeno?aiieyoe??th aeiciai? e?eai? ia cia/aiiy ieiu? eoiee, ye
iieacaii ia ?en. 5 aeey Bacillus mesentericus AONN 31029 ? Pseudomonas
aeruginosa ATCC 10145. I?i?iaeuei? ?ia?a?oi?i? eiioeaio?aoe?? AIAE ii
a?aeiioaiith aei ??cieo aaeoa??e i?eaaaeai? a oaaeeoe? 1.
Oaaeeoey 1.
Ae?y AIAE ia aaeoa???.
Iacaa ooaio aaeoa??? Cia/aiiy ?N* , ieI
Bacillus subtilis ATCC 6633 1,0 + 0,12
Bacillus mesentericus ATCC 31029 1,2 + 0,14
Staphylococcus aureus P-209 1,5 + 0,14
Staphylococcus aureus ATCC 25923 1,2 + 0,14
Micrococcus luteus ATCC 10240 16,0 + 1,20
Pseudomonas aeruginosa ATCC 10145 3,6 + 0,22
Escherichia coli K12 (l) 0,3 + 0,10
Escherichia coli ATCC 25922 >150
Proteus vulgaris ATCC 13315 100 – 150
sse aeaeii c oaaeeoe?, AIAE aeyaeany caaaeii a?eueo oiene/iei ii
a?aeiioaiith aei a?aiiiceoeaieo aaeoa??e, i?ae aei a?aiiaaaoeaieo, ca
aeiyoeii ooaio Escherichia coli K12 (l).
A aeaui aeueo eiioeaio?aoe?yo (100-200 ieI) AIAE i?eai?/o? ??no a?ea?a:
Fusarium graminearum, Penicillium griseus, Mucor plumbum. Ooia?oeeaeii?
ae?? ii a?aeiioaiith aei Candida albicans aeyaeaii ia aoei.
I?e aeine?aeaeaii? aieeao ??cieo eiioeaio?aoe?e AIAE ia
aooioinoi?eethaaiiy ?aoeaioi?a AO? a i?aia?aoao ieaciaoe/ieo iaia?ai
ee?oei e?i?? A431 iieacaii, ui aeiaeaaaiiy 200 iI iaioeaeo a i?iae
i?ecaiaeeoue aei cieaeaiiy ??aiy aooioinoi?eethaaiiy i?eiaeii? a aeaa
?ace. Aeaineoiiao??y ?aae?iaaoia?ao?a iieacaea, ui AIAE cae?enith?
oaeiae aieea (caeaa?eueoiai ?ia?a?oi?iee) ia oinoi?eethaaiiy ?ioeo
a?ee?a a i?aia?aoao iaia?ai ee?oei e?i?? A431.
?enoiie 6. ?aae?iaaoia?ao aooioinoi?eethaaiiy in vitro i?ioa?ie?iac: Lyn
(3, 4), Syk (5, 6) i PKCm (7, 8), ?ioiii?aoeei?oiaaieo a?aeiia?aeieie
aioeo?eaie. Aeey eiio?iey (1, 2) ?ioiii?aoeei?oaoe?th aeeiioaaee
aioeo?eaie Mab MOPC. A i?iaao 2, 4, 6, 8 oinoi?eethaaiiy i?iaiaeeeinue a
i?enooiino? 200 iI AIAE.
Aeey aeine?aeaeaiiy aieeao AIAE ia aeoeai?noue ?ioiii?aoeei?oiaaieo
oeeoicieueieo i?ioa?ie?iac eiai aeiaeaaaee a i?iae aei e?ioeaai?
eiioeaio?aoe?? 200 iI. Ca aeaieo oiia AIAE i?eai?/oaaa aeoeai?noue
aeine?aeaeoaaieo i?ioa?ie?iac: aeaio ?cioi?i Lyn (p56 – ia 70% ? p53 –
ia 42%), Syk – ia 20% ? PKCm – ia 91%. ?aae?iaaoia?ao, ui ?ethno?o?
i?eai?/aiiy aeoeaiino? oeeoicieueieo i?ioa?ie?iac a i?enooiino? AIAE,
iaaaaeaiee ia ?en. 6.
I?e aeine?aeaeai? i?ie?oa?aoeaii? aeoeaiino? eoeueoeaiaaieo ee?oei e?i?e
Namalwa (e?ioiia Aa?e?ooa ethaeeie) ? Jurkat (e?ioiaeanoi? O-ee?oeie
ethaeeie) ca ?iei?ii?aoe??th 3I-oei?aeeio anoaiiaeaii, ui aeiaeaaaiiy a
na?aaeiaeua ?ieoaaoe?? AIAE a eiioeaio?aoe?yo, aeueo 6o10-8 I,
i?ecaiaeeoue aei cieaeaiiy ??aiy neioaco AeIE a iiaeaeueieo ee?oeiao.
Aeiaeaaaiiy AIAE a eiioeaio?aoe?yo 10-8 – 5o10-8 I i?ecaiaeeoue aei
iaaaeeeiai, aea a??ia?aeiiai i?aeaeuaiiy ??aiy neioaco AeIE a ee?oeiao.
Eiioeaio?aoe?? AIAE, aeu? i?ae 5o10-6 I, aeeeeeaee oaeaeeo – i?ioyaii
e?eueeio oaeeei – caaeaaeue ee?oei.
I?i?iaeueio e?oe/io eiioeaio?aoe?th AIAE ii a?aeiioaiith aei
a?eo?ioeeo?a ethaeeie a iaoeo aeine?aeaeaiiyo aecia/aii ye 10-7 I.
?icae?e 6. Oiiae i?iaeoeoe?? AIAE.
Aeey ia?aa??ee i?eiouaiiy i?i ca’ycie nae?aoe?? eoeueoeaiaaieie
ee?oeiaie AIAE c ae??th e?aaiae?a ?aoeaioi?a AO? aoei canoiniaaii
oanooaaiiy na?aaeiaeu ?ieoaaoe?? ee?oei c ??ciei i?aaenoaaieoeoaii
?aoeaioi?a AO? ia aioei?e?iaio aeoeai?noue. Aoei aeine?aeaeaii
noia?iaoaioe ee?oei e?i?e KB, Colo320HSR, MCF-7, MEWO, CHO, Molt4, Raji,
ui ?ieoaoaaeenue a noaiaea?oieo oiiaao ? a i?enooiino? AO?. A
na?aaeiaeuao ?ieoaaoe?? ee?oei a?eueoino? aeine?aeaeaieo e?i?e
aioei?e?iaii? aeoeaiino? aeyaeaii ia aoei, ie??i e?i?e M-HeLa ? A431. A
ia?oeo aioei?e?iaia aeoeai?noue aeaoaeoo?oueny iino?eii ia iacia/iiio
??ai?. A na?aaeiaeu? ?ieoaaoe?? ee?oei e?i?? A431 iiyaa aioei?e?iaii?
aeoeaiino? ?iaeoeo?oueny ?ieoaaoe??th a i?enooiino? AO?.
I?e ia?iaoe? ee?oei oi?aieiaeie ao??aie, ui noaiaea?oii
aeei?enoiao?oueny aeey ?iaeoeoe?? nae?aoe?? aeaoainei?a a?aioeioeeoaie
(Chertov, 1996), iineeaiiy nae?aoe?? aioei?e?iaieo eiiiiiaio?a
iiaeaeueieie ee?oeiaie ia aeyaeaii, a a ee?oeiao e?i?? A431
niinoa??aa?oueny ?? iineaaeaiiy.
?icae?e 7. Aiae?c ? iaaiai?aiiy ?acoeueoao?a.
Aeoeai?noue oe?iceiiaeo i?ioa?ie?iac a?ae?a?a? cia/io ?ieue a i?ioeanao
ceiye?nii? o?ainoi?iaoe?? ? i?ia?an?? iooeei. O ca’yceo c oeei iiooe
aaaio?a, caeaoieo aeieoaaoe ia?aaea/o i?oiaaiiiai neaiaeo, iaoiiaeaio
aeoeai?noth i?ioa?ie?iac, iaaoaa? ana a?eueoi? aeooaeueiino?.
A ?acoeueoao? i?iaaaeaii? ?iaioe iaie aeae?eaii iaioeaeiee ?ia?a?oi?
i?ioa?ie?iac AIAE, ui ca nai?ie a?io?i?/ieie ? o?c?ieia?/ieie
aeanoeainoyie aeecueeee aei aeaoainei?a, ui i?iaeoeothoueny a ee?oeiao
e?noeiaiai iiceo ? iie?eaieo oeaiei nnaaoe?a. Iieacaii, ui nae?aoe?y
AIAE iiaea aooe ?iaeoeiaaia a iooeeiieo ee?oeiao i?e ?o noeioeyoe??
aiaeiaaiieie aai aeciaaiieie oaeoi?aie ?inoo.
Aeniiaee
C na?aaeiaeua ?ieoaaoe?? iooeeiieo ee?oei aeae?eaii a?ae?ioiaiee
iniiaiee iaioeae AIAE c iieaeoey?iith ianith aeecueei 3 eAe c
aeanoeainoyie ?ia?a?oi?a i?ioa?ie?iac ? aaeoa?eoeeaeiiai aaaioa.
Anoaiiaeaii, ui AIAE nae?aoo?oueny ee?oeiaie e?i?? A431 ? noae?i??
A431/1522 o a?aeiia?aeue ia noeioeyoe?th e?aaiaeaie ?aoeaioi?a AO? (AO?
? OO?a).
A ae?aiacii? eiioeaio?aoe?e 1-3 ieI AIAE i?eai?/o? ??no a?aiiiceoeaieo ?
aeayeeo a?aiiaaaoeaieo aaeoa??e. Aeu? eiioeaio?aoe?? iaioeaeo
i?eai?/othoue ??no a?aiiaaaoeaieo aaeoa??e ? a?ea?a.
A noai?e?iiiey?ieo eiioeaio?aoe?yo AIAE i?eai?/o? aeoeai?noue
oe?icei-niaoeeo?/ieo ? na?ei-o?aiiei-niaoeeo?/ieo i?ioa?ie?iac,
aeae?eaieo c ee?oei, ui na?ae/eoue i?i eiai iiaeeeao o/anoue a
?aaoeyoe?? ?inoo ee?oei.
AIAE i?eai?/o? neioac AeIE a iooeeiieo ee?oeiao in vitro, a a aenieeo
eiioeaio?aoe?yo – oeeoioiene/iee aeey ieo. AIAE oaeiae caeaoiee
aeeeeeaoe aaiie?c a?eo?ioeeo?a ethaeeie.
NIENIE IIOAE?EIAAIEO IAOEIAEO I?AOeUe
Iia?aaiie I.A., Aa?iai/oe E.A., Ia?eaaaa I.A., Oiaoa A.E., Na?ia N.I.,
Auei?ac A.E. Aeia?yeni?anney o?ainoi?ie?othuaai oaeoi?a ?inoa aeueoa
eeaoeaie I-HeLa/1522// Yenia?ei. iieie.- 1997.- 19, ?1.- N. 296-299.
Iia?aaiie I.A., Oiaoa A.E., Aa?iai/oe E.A., Ia?eaaaa I.A. Eiaeae?iaaiea
eeiaciie aeoeaiinoe ?aoeaioi?a YO? aeae?ioiaiui iaioeaeii, nae?aoe?oaiui
eeaoeaie A431/1522// Yenia?ei. iieie.- 1997.- 19, ?4.- N. 296-299.
Aa?iai/oe E.A., Oiaoa A.E., Ia?eaaaa I.A., Iia?aaiie I.A., Auei?ac A.E.
Eciaiaiea nioiioaiee iieaeoey?iuo oi?i o?ainoi?ie?othuaai oaeoi?a ?inoa
a e i?IE ?aoeaioi?a YO? i?e aaiaoieaioea?iaaiaca, eiaeooee?iaaiiii
N-ieo?iciaeeyoeeaieiii o e?un// Yenia?ei. iieie.- 1998.- 20, ?1.- N.
29-32.
Pogrebnoy P.V., Hobta A.I., Soldatkina M.A., Garmanchouk L.V., Markeeva
N.V., Eremenko T. A protein kinase inhibitor from A431 subline
overexpresing TGFa possesses antimicrobial activity// New Microbiol.-
1998.- 21, No.3.- P. 269-273.
Hobta A.I., Pogrebnoy P.V. Mammalian peptide antibiotics as regulatory
and anticancer agents. (Review). Exp. oncol.- 1998.- 20, No.3-4.- P.
170-179.
AIIOAOe?ss
Oiaoa A.?. Nae?aoe?y eoeueoeaiaaieie ee?oeiaie ai?aea?ii?aeii?
ea?oeeiiie iaioeaeo c aeanoeainoyie ?ia?a?oi?a i?ioa?ie?iac.- ?oeiien.
Aeena?oaoe?y ia caeiaoooy iaoeiaiai nooiaiy eaiaeeaeaoa a?ieia?/ieo iaoe
ca niaoe?aeuei?noth 14.01.07 – iieieia?y.- ?inoeooo aenia?eiaioaeueii?
iaoieia??, iieieia?? ? ?aae?ia?ieia?? ?i. ?.?.Eaaaoeueeiai IAI Oe?a?ie,
Oe?a?inueeee iaoeiai-aeine?aeiee ?inoeooo iieieia?? oa ?aae?ieia?? IIC
Oe?a?ie, Ee?a, 1999.
C na?aaeiaeu ?ieoaaoe?? ee?oei ai?aea?ii?aeii? ea?oeeiiie ethaeeie, ui
aeni?anothoue eAeIE aai o?ainoi?ioth/iai oaeoi?a ?inoo a, aeae?eaii
a?ae?ioiaiee iniiaiee iaioeae, iacaaiee AIAE, c iieaeoey?iith ianith
aeecueei 3 eAe. Anoaiiaeaii, ui nae?aoe?y AIAE ee?oeiaie e?i?e A431 ?
A431/1522 ?iaeoeo?oueny ae??th e?aaiae?a ?aoeaioi?a ai?aea?iaeueiiai
oaeoi?a ?inoo. Aeine?aeaeaii niaeo? a?ieia?/ii? aeoeaiino? aeae?eaiiai
iaioeaeo. A aeena?oaoe?? iieacaii ?ia?a?oi?io ae?th AIAE ia
i?ioa?ie?iace, a naia: ErbB (?aoeaioi? AO?), Lyn, Syk, PKCm. Aecia/aii
eiioeaio?aoe??, a yeeo AIAE i?eai?/o? ??no ?yaeo ooai?a aaeoa??e.
Iienai? cieaeaiiy ??aiy neioaco AeIE a eoeueoeaiaaieo iooeeiieo ee?oeiao
i?e ?ieoaaoe?? a i?enooiino? AIAE ? AIAE-iiina?aaeeiaaiee aaiie?c
a?eo?ioeeo?a ethaeeie in vitro.
Eeth/ia? neiaa: AIAE, ?ia?a?oi? i?ioa?ie?iac, ?aoeaioi? AO?.
SUMMARY
Hobta A.I. Secretion of the peptide possessing the inhibitory activity
towards the protein kinases by cultured epidermoid carcinoma cells.-
Manuscript.
Thesis for the degree of candidate of biological sciences on speciality
14.01.07 – oncology.- R.E.Kavetsky Institute of Experimental Pathology,
Oncology, and Radiobiology NAS of Ukraine, Institute of Oncology and
Radiology Ministry of Health Care of Ukraine, Kyiv, 1999.
From the conditioned media of human epidermoid carcinoma cells
expressing the transforming growth factor a cDNA gene, a hydrophobic
cationic peptide named ECAP with molecular weight nearly 3 kDa is
isolated. As it is established, the secretion of ECAP by A431 and
A431/1522 cell lines is induced by ligands of the epidermal growth
factor receptor. A spectrum of biological activities of the peptide is
investigated. The inhibitory activity of ECAP towards the protein
kinases namely ErbB (EGF receptor), Lyn, Syk, PKCm is shown. The growth
inhibitory concentrations of ECAP relatively the different strains of
bacteria are determined. Also suppression of DNA synthesis in cultured
tumor cells in presence of ECAP and ECAP-mediated induction of
erythrolysis in vitro is described.
Key words: ECAP, inhibitor of the protein kinases, EGF receptor.
AIIIOAOeEss
Oiaoa A.E. Nae?aoeey eoeueoeae?oaiuie eeaoeaie yieaea?iieaeiie
ea?oeeiiiu iaioeaea ni naienoaaie eiaeaeoi?a i?ioaeieeiac.- ?oeiienue.
Aeenna?oaoeey ia nieneaiea o/?iie noaiaie eaiaeeaeaoa aeieiae/aneeo iaoe
ii niaoeeaeueiinoe 14.01.07 – iieieiaey.- Einoeooo yenia?eiaioaeueiie
iaoieiaee, iieieiaee e ?aaeeiaeieiaee ei. ?.A.Eaaaoeeiai IAI Oe?aeiu,
Oe?aeineee iao/ii-enneaaeiaaoaeueneee einoeooo iieieiaee e ?aaeeieiaee
IC Oe?aeiu, Eeaa, 1999.
Ia?yaeo n iieeiaioeaeiuie oaeoi?aie ?inoa, iiooieaaua eeaoee
i?iaeooee?otho ?yae oaeoi?ia, oaiaoathueo i?ieeoa?aoeeth eeaoie.
Oaeiaiie yenia?eiaioaeueiie iiaeaeueth aeey eco/aiey nae?aoeee iaaeo
a?oii oaeoi?ia yaeythony eoeueoo?u iiooieaauo eeaoie. ?aiaa i?e
eniieueciaaiee iaoiaeia aaiiie eiaeaia?ee iaie auee iieo/aiu eeaoi/iua
noaeeiee A431/1522 e M-HeLa/1522, eioi?ua oa?aeoa?ecothony aieaa
ceiea/anoaaiiui oaiioeiii, ii-n?aaiaieth n eeieyie-i?aaeoanoaaiieeaie,
iineieueeo yeni?anne?otho eAeIE aai o?ainoi?ie?othuaai oaeoi?a ?inoa a,
aaaaeaiiue i?e iiiiue ?ao?iae?oniiai aaeoi?a.
A ?acoeueoaoa enneaaeiaaiey aeeyiey i?aia?aoia n?aae eieoaaoeee
iiooieaauo eeaoie ?aciuo eeiee ia oinoi?eee?iaaiea in vitro a i?aia?aoao
ieaciaoe/aneeo iaia?ai eeaoie eeiee A431 a ?yaea neo/aaa iieacaia eo
niiniaiinoue oaiaoaoue oinoi?eee?iaaiea ?aoeaioi?a YO?. Iaeaieaa
au?aaeaiiui eiaeaeoi?iue yooaeo ii ioiioaieth e i?ioaeieeiaciie
aeoeaiinoe YO?-? ieacaeny a n?aaeao eieoaaoeee eeaoie noaeeiee
A431/1522, i?iaeooee?othueo ?aeiiaeiaioiue OO?a. Iinea o?aeoeeiie?iaaiey
iaioeaeiuo eiiiiiaioia eiiaeeoeeiie?iaaiiuo n?aae ieacaeinue, /oi
o?aeoeey, eiaeae?othuay aooioinoi?eee?iaaiea YO?-?, ia iaeaaeaao
YO?-eiieo?aioiie aeoeaiinoueth e, eae iieacaee ?acoeueoaou
oinoi?eee?iaaiey n eniieueciaaieai ianiethaeeece?iaaiiuo iaia?aiiuo
aaceeoe, niiniaia e acaeiiaeaenoaeth n eeieaeiuie iaia?aiaie.
Ia iniiaaiee iieo/aiiuo ?acoeueoaoia auei auaeaeiooi i?aaeiieiaeaiea i
aiiieiaee iaioeaeiiai eiaeaeoi?a i?ioaeieeiacu ?aoeaioi?a YO?
aeaoaineiai – a?oiia aioeiee?iaiuo iaioeaeia ieaeiieoathueo.
I?iaaaeaiiia oanoe?iaaiea ia aaeoa?eyo auyaeei i?yioth ei??aeyoeeth
iaaeaeo aaeoa?eoeeaeiie aeoeaiinoueth i?aia?aoia e eo eiaeaeoi?iui
aeaenoaeai ia i?ioaeieeiacioth aeoeaiinoue ?aoeaioi?a YO?.
I?e iiiiue o?iiaoia?aoe/aneeo i?ioeaaeo? ec n?aae eieoaaoeee eeaoie
noaeeiee A431/1522 auaeaeai aeae?ioiaiue iniiaiue iaioeae ni naienoaaie
eiaeaeoi?a i?ioaeieeiac e aaeoa?eoeeaeiiai aaaioa. I?e yeaeo?ioi?aca a
?aaeooee?othueo oneiaeyo auaeaeaiiue iaioeae ii?aaeaeyaony aaeeinoaaiiie
ciiie n yeaeo?ioi?aoe/aneie iiaeaeaeiinoueth, niioaaonoaothuae
iieaeoey?iie ianna ieiei 3 eAe. Aeey iaioeaea i?aaeeiaeaii iacaaiea AIYE
(aioeiee?iaiue iaioeae ec eeaoie yieaea?iieaeiie ea?oeeiiiu).
A ?acoeueoaoa enneaaeiaaiee niaeo?a aeieiae/aneie aeoeaiinoe
auaeaeaiiiai iaioeaea iieacaii aai eiaeaeoi?iia aeaenoaea ia
i?ioaeieeiacu, a eiaiii ErbB (?aoeaioi? YO?), Lyn, Syk, PKCm a ?aaeoeee
aooioinoi?eee?iaaiey in vitro. Ii?aaeaeaiu eiioeaio?aoeee, a eioi?uo
AIYE oaiaoaao ?ino ?yaea ooaiiia a?aiiieiaeeoaeueiuo e
a?aiio?eoeaoaeueiuo aaeoa?ee. E?iia oiai, iienaii nieaeaiea o?iaiy
neioaca AeIE a eoeueoeae?oaiuo iiooieaauo eeaoeao eeiee Namalwa e Jurkat
i?e eieoaaoeee a i?enoonoaee AIYE e AIYE-iiin?aaeiaaiiue aaiieec
y?eo?ioeeoia /aeiaaea in vitro.
Onoaiiaeaii, /oi AIYE nae?aoe?oaony eeaoeaie eeiee A431 e noaeeiee
A431/1522 a ioaao ia noeioeyoeeth eeaaiaeaie ?aoeaioi?a yieaea?iaeueiiai
oaeoi?a ?inoa (YO? e OO?a), i?e/?i ia?aaioea eeaoie oi?aieiauie yoe?aie
i?aiyonoaoao nae?aoeee AIYE.
Eeth/aaua neiaa: AIYE, eiaeaeoi? i?ioaeieeiac, ?aoeaioi? YO?.
* ?N – i?i?iaeueia eiioeaio?aoe?y, ui i?eai?/o? ??no aaeoa??e
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