- Email: [email protected]
Defence mechanisms in free radical induced toxicities
1 and B lvmphocvte mitcgens WB,B measwed Finally. we dnermined anti tetanus-toxin and enti d~ohtheffa4oxin antibodv levels befan and after ba03t.w ~ccinetion {et i&ten yarrs since last fomgoinp veccfnalani.AsecondsstotbImd specimenswas col~tsdtwbyaen lfte, the lint set. Pmfiminwv st~isticel an&see indicate eqnif&nt coneIeUOnf fp-xitiva 0, negative] between Iev~ls of PCDD/PCDFIPCB and sow mitoaen response parameters. immunoalobulin kwfs. and autoanbbodies. and e tendency towwds reduced B-lymphocyte ma&e,s ee measured by flow cv?ome~~ In addition. a tendency towe,ds e co,relation b&wan PCODIPCDF levels end sonw vaccinelion ,eswnse parameters wes obse,ved. Kwwwds; dioxin; PCB: contaminated mY”el”“ttb”
cywdllm
in Lung
seatood: human expoewe:
im-
Rbmml*
Yw% Maninel. Ohtie, M6nard. Pierre Veillam. Jean-Micbel Vignaud. Nadine Maninet INSERMUY c-o. tin 10. and f~dbrsaon MBdicPChirurgicak de fheumolog!e, CHU de Nancy 5451 t NancylYanUaeuMe. FRwr~e Fbroais is a pathological process cheracterized bv the replacement of nomel tissue bv mesenshvmal cells and the ext,ecelfula, matrix pm. duced by these cells. The sequence of events leading to fibrosis d an organ inwlves,the subsequent processes of injury wth mflammation end derangement of ihs normal t,s.we architecture. followed bv tissue repair with OCEY. mulation 01 mesenchymal cells in the area of derangement The same sequence of events OECIIIS in wound healing with normal granulation t155ue and see, tomx.tian. but, while normal see, fwmation is vec( localized and transient. in wntmst. in fibrosis. the repair process 1s exaaaerawd and usuallv wdespread anc1 can be chronic. lollammerory cells fmaw mononuclear phawcvtesl. platelets. endothelial celk.. and lvpe II pneumocvtes play a dlrett and Indirect role m tissue injwv and repair The evaluation of three bums” fibmtic lung diseeres.twoddfuse [,diocathic ~lmonarylibrosis(lPF]. and the adult reepiratw distress svndmme lARDSIt. and one local (tumor $l,orne in lung cancer], has shown thal several cylokines participate to the local injury and inllammafon/ reaction jinte,kuUn-1 01.1).interlsukin-8 (IL81. monocrte chemotactic prtltein-1 (MCP-I). tunm, necrosis factor-0 ITNF4 while olher cytokines are mvobed m tissue repair Iplateletdsrwed gratih lacto, IPDGFI. insulin like growth factor-1 IIGF-I], end transforming growth tactor-p ITOF-pt]. A better understanding of the cyrokines and cytokine networks involved in lung fibrosis leads to the possibilii of new therapeutic ap proaches.
Cesare Manlecucco. G. Sehiavo. 0. Ross&to. B. Pxxdain t di Scienle Biomediche. UniuersiMdi Padova. Lb; I leboramira ds Neu,obioio$~a du CNRS, Gil-swrvene, Flsnce
Dlpsmmsnm
TetanuslTeNT]and botulinurn newotoxlns IBoNT. seven diiesmt~ A-G] we reapDnsibla ot the neu,opa?aly(ic syndramw of tetanre end bOfulism. ,esDtetiwlv. They of two disullide-linked polvpeptide chain% 1 100 kDa chain ir inwfued in nsuraspecific binding and cell penetrstiin of the tight chain L (50 kDa). whch is responsible 1~ the blmkede ot neumtransmitt~, release. The L chain of TeNT and BoNTs are ziwendopeptidases specific forthme proteins of synaptic terminals inwhred ti nsumex~osis: VAMf? SNAP-25 ed syntenn. 1eNT and BoNTB. ID. I? and IG cleave VAMP It daferent single peptide !xnde. BoNT::, and A we specific fur two peptde bonds of SNAP.25 arid IC cIee”es nlnts*in]!]. Thesg ,%““sf”di~telh~tVAMF! SNAP-25 end syntax,” p!ava key role in zrwoerocvtosiis. Thsre thiaa protams have been pmposed by Rothman 121to be responsible to, the process of syneptiiveeicfe dockingtotheactive~onesol thepresvnaptfc mem. branss.Theneumloxinspecifieityirduetoadoublerecagnitlan~~:heir three targets via. al the segment I0 be cleaved end bl e nsumtoxin binding motif common to VAMP! SNAP-25 andsynterin
consist
I,, MOmbSUCcD.c e sckl*Y..G. I1ewMd 12, R0lhmm. J E ,lewN~twrw2 55.83
MFlwwol. 8. I-13
J.F. Nagelkerke. B. wn de Water. M KruiderinQ Laidantdmstudam Ceniw for Drug Research. Div of Kwicolo~ L&an “nwarwh: PoBox 9503,.?3W RA Leiden, 7he Naherlands Mosl nsphrotoxic compounds. such es drugs end Industtil cornpounds. exe* their noxiow effect in a specific region of the kidney. Within the kidney. the pmrlmal tubular cefls fPTC] are exposed to the highest concentmtions of xenabiotks due to their transpwtina. cow cemratina and drug metabolizing abilities. Thewiwe nephrotoxicity is best studied in these parlicubr cells. Much in~ormalion about cellula, mechanismsot nephrotoaicilvhasbeenobrained ueingtmehlyieoleted pmxlmaltubular materialfrom rscs and rabbis. In general. with rats& lated PIG 8,e used and with rabbits micwdissected whole tub&s. Both prepwatnrns ciln be brought into culture for long term sxposwe sadies. In the past five veers we have specialisad m studies I,, indntduel Iwing 0, fued cell using vidw microscopy. confocal lew scsn microscopy and flow cytometry. !s these techniques the ffua,~catce of probes o, antibodies IS used lo meaaurebiochemi~lparameten ordetect the cellular loc4lizetion ot lhe plabe. A large veriery ticchemical parameters is available nawadavs and devebpment has become e specific branch d science. In principle a fluo,escent tea can be attached to eve”/ anbbody and therefore cellular lacalieadon of evenl t~p.3 of antibody is passible. Ths s1,ona pOint of video microscopy is that multiple pxemelers cm be studied within one cell and in this way it is possible to mahe correlalions between pawnewe 1.0. sep arate causes from consequences. With convenlional Rwxescence mC crocopvthe image is ahraw blurred due10 out4lwus tluorsscence. With confocal law seen microscopy lhis fluoresCence is not recorded anC therefore cnsp images areablawed. In addition because e laser k usedaseliQhtsau,ee. imagesfrom befowlhesurtaceof thespecimen can beobtalned In general. in bklogieal tissue it ispossibletovisuakr planes as deep as 120 pm. With flaw-cytomet~ 3 psrameten ,n every cell are recorded and the recording of a few thousands of cells takes no more than 10 secondo. Management of the enormous amount ot data that is generat%d; is through use&end,” sofw,a,e.
d probes lor
Free radicals. primarily oxygen derived. have been suogeswd lo be in. valved in D number of diseases including nsuredsgeneratlondiaeasss. chronn: inflammalory diseases. cardiovascular dtseases and canoe,, The molecular mechanisms behind the free radical effects are no1 known but interaction with lipids, protem o, DNA may all be of importanc%. Several anboxldant delence systems exists: Enlymatii systems including supemxiddismutase catalase and glutalhione peroxidase, nonemwnatie system including vitamin E. vitamin C. &carotene lyf~pene end ubquinone and metal chelators such as tr.enSfe,,in end lacloferrin. There is often an interaction between the dIfferen! amioxidam dafence svste,x. The presentebon will tn, 10 review our cwent knavledae waardma 0urendaaenous anliovidanldefsnce svs1ems~s well asdiscusspossibiliiies of using exoaenousantior,dants in strengtheningthis defence.
cywdllm
in Lung
seatood: human expoewe:
im-
Rbmml*
Yw% Maninel. Ohtie, M6nard. Pierre Veillam. Jean-Micbel Vignaud. Nadine Maninet INSERMUY c-o. tin 10. and f~dbrsaon MBdicPChirurgicak de fheumolog!e, CHU de Nancy 5451 t NancylYanUaeuMe. FRwr~e Fbroais is a pathological process cheracterized bv the replacement of nomel tissue bv mesenshvmal cells and the ext,ecelfula, matrix pm. duced by these cells. The sequence of events leading to fibrosis d an organ inwlves,the subsequent processes of injury wth mflammation end derangement of ihs normal t,s.we architecture. followed bv tissue repair with OCEY. mulation 01 mesenchymal cells in the area of derangement The same sequence of events OECIIIS in wound healing with normal granulation t155ue and see, tomx.tian. but, while normal see, fwmation is vec( localized and transient. in wntmst. in fibrosis. the repair process 1s exaaaerawd and usuallv wdespread anc1 can be chronic. lollammerory cells fmaw mononuclear phawcvtesl. platelets. endothelial celk.. and lvpe II pneumocvtes play a dlrett and Indirect role m tissue injwv and repair The evaluation of three bums” fibmtic lung diseeres.twoddfuse [,diocathic ~lmonarylibrosis(lPF]. and the adult reepiratw distress svndmme lARDSIt. and one local (tumor $l,orne in lung cancer], has shown thal several cylokines participate to the local injury and inllammafon/ reaction jinte,kuUn-1 01.1).interlsukin-8 (IL81. monocrte chemotactic prtltein-1 (MCP-I). tunm, necrosis factor-0 ITNF4 while olher cytokines are mvobed m tissue repair Iplateletdsrwed gratih lacto, IPDGFI. insulin like growth factor-1 IIGF-I], end transforming growth tactor-p ITOF-pt]. A better understanding of the cyrokines and cytokine networks involved in lung fibrosis leads to the possibilii of new therapeutic ap proaches.
Cesare Manlecucco. G. Sehiavo. 0. Ross&to. B. Pxxdain t di Scienle Biomediche. UniuersiMdi Padova. Lb; I leboramira ds Neu,obioio$~a du CNRS, Gil-swrvene, Flsnce
Dlpsmmsnm
TetanuslTeNT]and botulinurn newotoxlns IBoNT. seven diiesmt~ A-G] we reapDnsibla ot the neu,opa?aly(ic syndramw of tetanre end bOfulism. ,esDtetiwlv. They of two disullide-linked polvpeptide chain% 1 100 kDa chain ir inwfued in nsuraspecific binding and cell penetrstiin of the tight chain L (50 kDa). whch is responsible 1~ the blmkede ot neumtransmitt~, release. The L chain of TeNT and BoNTs are ziwendopeptidases specific forthme proteins of synaptic terminals inwhred ti nsumex~osis: VAMf? SNAP-25 ed syntenn. 1eNT and BoNTB. ID. I? and IG cleave VAMP It daferent single peptide !xnde. BoNT::, and A we specific fur two peptde bonds of SNAP.25 arid IC cIee”es nlnts*in]!]. Thesg ,%““sf”di~telh~tVAMF! SNAP-25 end syntax,” p!ava key role in zrwoerocvtosiis. Thsre thiaa protams have been pmposed by Rothman 121to be responsible to, the process of syneptiiveeicfe dockingtotheactive~onesol thepresvnaptfc mem. branss.Theneumloxinspecifieityirduetoadoublerecagnitlan~~:heir three targets via. al the segment I0 be cleaved end bl e nsumtoxin binding motif common to VAMP! SNAP-25 andsynterin
consist
I,, MOmbSUCcD.c e sckl*Y..G. I1ewMd 12, R0lhmm. J E ,lewN~twrw2 55.83
MFlwwol. 8. I-13
J.F. Nagelkerke. B. wn de Water. M KruiderinQ Laidantdmstudam Ceniw for Drug Research. Div of Kwicolo~ L&an “nwarwh: PoBox 9503,.?3W RA Leiden, 7he Naherlands Mosl nsphrotoxic compounds. such es drugs end Industtil cornpounds. exe* their noxiow effect in a specific region of the kidney. Within the kidney. the pmrlmal tubular cefls fPTC] are exposed to the highest concentmtions of xenabiotks due to their transpwtina. cow cemratina and drug metabolizing abilities. Thewiwe nephrotoxicity is best studied in these parlicubr cells. Much in~ormalion about cellula, mechanismsot nephrotoaicilvhasbeenobrained ueingtmehlyieoleted pmxlmaltubular materialfrom rscs and rabbis. In general. with rats& lated PIG 8,e used and with rabbits micwdissected whole tub&s. Both prepwatnrns ciln be brought into culture for long term sxposwe sadies. In the past five veers we have specialisad m studies I,, indntduel Iwing 0, fued cell using vidw microscopy. confocal lew scsn microscopy and flow cytometry. !s these techniques the ffua,~catce of probes o, antibodies IS used lo meaaurebiochemi~lparameten ordetect the cellular loc4lizetion ot lhe plabe. A large veriery ticchemical parameters is available nawadavs and devebpment has become e specific branch d science. In principle a fluo,escent tea can be attached to eve”/ anbbody and therefore cellular lacalieadon of evenl t~p.3 of antibody is passible. Ths s1,ona pOint of video microscopy is that multiple pxemelers cm be studied within one cell and in this way it is possible to mahe correlalions between pawnewe 1.0. sep arate causes from consequences. With convenlional Rwxescence mC crocopvthe image is ahraw blurred due10 out4lwus tluorsscence. With confocal law seen microscopy lhis fluoresCence is not recorded anC therefore cnsp images areablawed. In addition because e laser k usedaseliQhtsau,ee. imagesfrom befowlhesurtaceof thespecimen can beobtalned In general. in bklogieal tissue it ispossibletovisuakr planes as deep as 120 pm. With flaw-cytomet~ 3 psrameten ,n every cell are recorded and the recording of a few thousands of cells takes no more than 10 secondo. Management of the enormous amount ot data that is generat%d; is through use&end,” sofw,a,e.
d probes lor
Free radicals. primarily oxygen derived. have been suogeswd lo be in. valved in D number of diseases including nsuredsgeneratlondiaeasss. chronn: inflammalory diseases. cardiovascular dtseases and canoe,, The molecular mechanisms behind the free radical effects are no1 known but interaction with lipids, protem o, DNA may all be of importanc%. Several anboxldant delence systems exists: Enlymatii systems including supemxiddismutase catalase and glutalhione peroxidase, nonemwnatie system including vitamin E. vitamin C. &carotene lyf~pene end ubquinone and metal chelators such as tr.enSfe,,in end lacloferrin. There is often an interaction between the dIfferen! amioxidam dafence svste,x. The presentebon will tn, 10 review our cwent knavledae waardma 0urendaaenous anliovidanldefsnce svs1ems~s well asdiscusspossibiliiies of using exoaenousantior,dants in strengtheningthis defence.