생명과학회지 (Journal of Life Science)

  • 제12권4호
  • /
  • Pages.452-459
  • /
  • 2002
  • /
  • 1225-9918(pISSN)
  • /
  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지
DOI QR코드

DOI QR Code

호중구의 자연 세포사멸 및 세포사멸 지연에 대한 Brefeldin A의 영향

Effects of brefeldin A on spontaneous and delayed apoptosis of human neutrophils

  • 김재석 (동아대학교 의과대학 내과학교실) ;
  • 이민정 (동아대학교 의과대학 생화학교실) ;
  • 이창민 (동아대학교 의과대학 미생물학교실) ;
  • 이상화 (동아대학교 의과대학 미생물학교실) ;
  • 배외식 (동아대학교 의과대학 생화학교실) ;
  • 곽종영 (동아대학교 의과대학 생화학교실)
  • 발행 : 2002.08.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

호중의 세포사멸은 자연적으로 일어나지만 여러 자극에 의한 신호에 의하여 증가하거나 지연된다. 본 연구에서는 세포 내 단백질 분비과정을 억제한다고 알려진 BFA가 호중구의 자연 세포사멸 및 세포사멸 지연에 어떠한 기작으로 작용하는가를 연구하였다. 호중구의 세포사멸은 사람 말초 혈액으로부터 분리하여 세포 배양 20시간 후 형태 변화, annexin V and propidium iodide의 염색, 및 DNA 전기영동 등으로 조사하였다. BFA는 농도 의존형으로 호중구의 세포사멸을 증가시킨다. CM-CSF나 LPS에 의한 세포사멸의 지연도 BFA에 의하여 억제되었다. 그러나 BFA의 영향은 db-cAMP, dexamethasone, 및 IL-8을 처리한 세포에서는 큰 영향을 받지 않았다. PKC-5의 억제제인 rottlerin에 의한 세포사멸의 지연은 BFA에 의하여 감소하였다. 그러나 BFA에 의한 세포사멸의 유도는 caspase-3 억제제인 zDEVD-fmk에 의하여는 영향을 받지 않았다. 한편, 세포사멸 억제에 관여하는 Mcl-1 단백질의 발현은 BFA의 처리에 의하여 감소하였다. 이들 결과들은 세포 내 단백질 분비 과정의 억제가 호중구의 세포사멸에 관여하며 이들의 작용은 Mcl-1 발현의 조절에 의한다는 것을 제시하고 있다.

Neutrophil apoptosis is a constitutive process that can be enhanced or delayed by various stimuli. In this study, effect of brefeldin A (BFA), which affects biological process of secretion, on constitutive and delayed apoptosis of neutrophils was investigated. Neutrophil apoptosis was determined after culturing for 20 hr in vitro by morphological changes, annexin V staining and DNA electrophoresis. BFA increased the constitutive apoptotic rate of neutrophils in dose-dependent manner. The delay of apoptosis induced by granulocyte macrophage-colony stimulating factor and lipopolysaccharide was also blocked by 10 $\mu$M of BFA. However, this effect of BFA was less marked when neutrophils were treated with dexamethasone, interleukin-8, or dibutyryl-cAMP. Moreover, the delay of neutrophil apoptosis induced by rottlerin, a specific inhibitor of protein kinase C-$\delta$ was significantly abrogated by BFA. Although BFA-induced apoptosis was not blocked by the caspase-3 inhibitor, zDEVD-fmk, expression levels of myeloid cell leukemia-1 (Mcl-1) were down-regulated by BFA. These results suggest that derangement of vesicular protein transport may be involved in the apoptosis of neutrophils, and that the action of BFA on apoptosis is dependent on changes in the expression of Mcl-1.

키워드

참고문헌

  1. FEBS Lett. v.487 Molecular control of neutrophil apoptosis Akgul,C.;D.A.Moulding;S.W.Edwards https://doi.org/10.1016/S0014-5793(00)02324-3
  2. Apoptosis v.6 Casepase-indepent apoptotic pathways in T lymphocytes Bidere,N.;A.Senik https://doi.org/10.1023/A:1011390103783
  3. Biochem.Biophys.Res.Commun v.249 A1 is a consititutive and inducible Bcl-2 homologue in mature human neutrophils Chuang,P.I.;E.Yee;A.Karasan;R.K.Winn;J.M.Harlan https://doi.org/10.1006/bbrc.1998.9155
  4. Nature v.360 Brefeldin a inhibits Golgi membrance-catalysed exchange of guanine nuceotide onto ARF proteni Donaldson,J.G.;G.D.Finazzi;R.D.Klausner https://doi.org/10.1038/360350a0
  5. Blood v.92 Involvement of caspases in neutrophil apoptosis:regulation by reactive oxygen species Fadeel,B.;A.Ahlin;J.Henter;S.Orrenius;M.B.Hampton
  6. Exp.Cell.Res Brefeldin A-mddiated apoptosis requires the activation of caspases and is inhibited by Bcl-2 Guo,H.;T.V.Tittle;H.Allen;R.T.Maziarz https://doi.org/10.1006/excr.1998.4235
  7. Clin.Sci(Colch) v.83 Resolution of acute inflammation and the role of apoptosis in the tissue fate in granulocytes Haslett,C.
  8. Nature v.360 Inhibition by brefeldin A of a Golgi membrance enzyme that catalyses exchange of guanine nuceotide bound to ARF. Helms,J.B.;J.E.Rothman https://doi.org/10.1038/360352a0
  9. Blood v.84 Differential experssion of bcl-2 and susceptibility ot anti-Fas-mediated cell death in peripheral blood lymphocytes, monocytes, and neutrophils Iwai.K.;T.Miyawaki;T.Takizawa;A.Konno;K.Ohta;A.Yachie,H.Seki;N.Taniguchi
  10. Blood v.94 Caspase-mediated proteolysis and activation of protein kinase Cδ play a central role in neutrophi apoptosis Khwaja,A.;L.Tatton
  11. J.Cell Biol. v.116 Brefeldin A: insights into the control of membrane traffic and organelle structure Klausner.R.D.;J.G.Donaldson;J.Lippincott Schwartz https://doi.org/10.1083/jcb.116.5.1071
  12. Proc.Natl.Acad.Sci.USA v.90 MCL1, a gene expressed in programmed myeloid cell differntiation, has sequence simmilarity to BCL2 Kozopas,K.M.;T.Yang;H.L.Buchan;P.Zhon;R.W.Craig https://doi.org/10.1073/pnas.90.8.3516
  13. Am.J.Pathol v.146 Immunohistochemical analysis of Mcl-1 protein in human tissues.Differential regylation of Mcl-1 and Bcl-2 protein production suggests a unique role for Mcl-1 in control of programmed cell death in vivo Krajewski.S.;S.Bodrucg;M.Krajewska;A.Shabaik;R.Gascoyne;K.Berean.J.C.Reed
  14. Hum.Reprod. v.17 2002 Modulation of neutrophil apoptosis vy plasma and peritoneal fluid from patients with advanced endometriosis Kwak,J.Y.;S.W.Park;K.H.Kim,Y.J.Na;K.S.Lee https://doi.org/10.1093/humrep/17.3.595
  15. J.Biol.Chem v.270 ADP-ribosylation factor functions synergistically with a 50-kDa cytosolic factor in cell-free activation of human neutrophil phospholipase D. Lambeth.J.D.;J.Y.Kwak,E.Bowman;D.Perry;D.Uhlinger;I.Lopez https://doi.org/10.1074/jbc.270.6.2431
  16. J.Leukoc.Biol. v.68 The loss of Mcl-1 expression in human polymorphonuclear leukocytes promotes apoptosis Leuenroth,S.J.;P.S.Grutkoski;A.Ayala;H.H.Simms
  17. Cell Growth Differ v.7 Activation of the sphingomyelin cycle by brefeldin A: effects of brefeldin A on differentiation and implications for a role for ceramide in regulation of protein trafficking Linardic,C.M.;S,Jayadev;Y.A.Hunnum
  18. Immunol.Today v.13 Poly's lament: the neglected role of the polymorphonuclear neutrophil in th afferent limb of the immune response Lloyd,A.R.;J.J.Pppenheim https://doi.org/10.1016/0167-5699(92)90121-M
  19. Blood v.92 Mcl-1 expression in human neutrophils:regulation by cytokines and correlation with cell survival Moulding,D.A.;J.A.Quayle;C.A.Hart;S.W.Edwards
  20. FEBS Lett. v.519 Anti-apoptotic role of phospholipase D in spontaneous and delay apoptosis of human neutrophils Park.M.A.;M.J.Lee;S.H.Lee;D.K.Jung;J.Y.Kwak https://doi.org/10.1016/S0014-5793(02)02705-9
  21. J.Biol.Chem v.274 Spontaneous neutrophil apoptosis involves caspase 3-mediated activation of protein kinase C-δ Pongraces,J.;P.Webb;K.Wang;E,Deacon,O.J.Lunn;J.M.Lord https://doi.org/10.1074/jbc.274.52.37329
  22. J.Biol.Chem v.276 Coupling endoplasmic reticulum stress to the cell death program.Mechanism of caspase activation Rao,R.V.;E.Hermel;S.Castro-Obregon;G.del Rio;L.M.Ellerby;H.M.Ellerby;D.E.Bredesen https://doi.org/10.1074/jbc.M102225200
  23. Clin.Sci.(Colch) v.83 Macrophage recognition of senescent neutrophils Savill,J.
  24. Semin.Cell Biol v.6 Granulocyte clearance by apoptosis in the resolution of inflammation Savill,J.C,Haslett
  25. Exp.Cell.Res v.227 Brefeldin A is a potent inducer of apoptosis in human cancer cells independently of p53 Shao.R.G.;T.Shimizu;Y.Pommier https://doi.org/10.1006/excr.1996.0266
  26. J.Leukoc.Biol v.57 Apoptosis in leukocytes Squier,M.K.;A.J.Sehnert;J.J.Cohen
  27. J.Urol v.164 Brefeidin A induces p53-independent apotosis in primary cultures of human prostatic cancer cells Wallen,E.;R.G.Sellers;D.M.Peehl https://doi.org/10.1016/S0022-5347(05)67323-5
  28. Trends Pharmacol.Sci v.20 Pharmacological manipulation of granulocyte appotosis:potential therapeutic targets Ward,C.;I.Drasfield;E.R.Chilvers,I.Haslett;A.G.Rossi https://doi.org/10.1016/S0165-6147(99)01391-7