• 四川大學(xué)華西醫(yī)院呼吸內(nèi)科（四川成都 610041）;

急性肺損傷/急性呼吸窘迫綜合征（ALI/ARDS）是指心源性以外的各種肺內(nèi)外致病因素導(dǎo)致的原發(fā)或繼發(fā)的急性、進行性呼吸衰竭，其病理改變主要表現(xiàn)為肺上皮及內(nèi)皮細胞的損傷、炎性浸潤和透明膜形成，并伴有肺間質(zhì)纖維化。臨床表現(xiàn)為以呼吸窘迫、頑固性低氧血癥和非心源性肺水腫為特征的一種急性進行性呼吸困難。采用常規(guī)的治療難以糾正其低氧血癥，死亡率高達60%，嚴重威脅人們的生命健康[1]。自1967年Ashbaugh及其同事首次描述ALI/ARDS以來，醫(yī)學(xué)研究者進行了大量關(guān)于ALI/ARDS發(fā)病機制及病理生理學(xué)的基礎(chǔ)及臨床研究，但是迄今ALI/ARDS的發(fā)病機理仍未完全闡明。近年來越來越多的研究提示凋亡因子（Fas/Fas配體，即Fas/FasL）介導(dǎo)的細胞凋亡在ALI/ARDS的發(fā)生發(fā)展過程中有著十分重要的作用[2，3]。本文就Fas/FasL的生物學(xué)特性及其在ALI/ARDS發(fā)病機制中的作用作一綜述。

引用本文： 蔣飛,范紅. Fas/FasL系統(tǒng)在急性肺損傷致病機制中的研究進展. 中國呼吸與危重監(jiān)護雜志, 2007, 6(2): 145-147. doi: 復(fù)制

1. Ware LB，Matthay MA.The acute respiratory distress syndrome.N Engl J Med，2000，342：1334-1349.
2. Matute-Bello G，Winn RK，Jonas M，et al.Fas (CD95) induces alveolar epithelial cell apoptosis in vivo：implications for acute pulmonary inflammation.Am J Pathol，2001，158：153-161.
3. Kitamura Y，Hashimoto S，Mizuta N，et al.Fas/FasL-dependent apoptosis of alveolar cells after lipopolysaccharide-induced lung injury in mice.Am J Respir Crit Care Med，2001，163：762-769.
4. Perl M，Chung CS，Ayala A.Apoptosis.Crit Care Med，2005，33：S526-S529.
5. French LE，Tschopp J.Protein-based therapeutic approaches targeting death receptors.Cell Death Differ，2003，10：117-123.
6. Wajant H.Death receptors.Essays Biochem，2003，39：53-71.
7. Suda T，Takahashi T，Golstein P，et al.Molecular cloning and expression of the Fas ligand，a novel member of the tumor necrosis factor family.Cell，1993，75：1169-1178.
8. Itoh N，Yonehara S，Ishii A，et al.The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis，Cell，1991，66：233-243.
9. Peter ME，Krammer PH.The CD95 (APO-1/Fas) DISC and beyond.Cell Death Differ，2003，10：26-35.
10. Scaffidi C，F(xiàn)ulda S，Srinivasan A，et al.Two CD95 (APO-1/Fas) signaling pathways.EMBO J，1998，17：1675-1687.
11. Korsmeyer SJ，Wei MC，Saito M，et al.Pro-apoptotic cascade activates BID，which oligomerizes BAK or BAX into pores that result in the release of cytochrome c.Cell Death Differ，2000，7：1166-1173.
12. Jimenez MF，Watson RW，Parodo J，et al.Dysregulated expression of neutrophil apoptosis in the systemic inflammatory response syndrome.Arch Surg，1997，132：1263-1269.
13. Matute-Bello G，Liles WC，Radella F 2nd，et al.Neutrophil apoptosis in the acute respiratory distress syndrome.Am J Respir Crit Care Med，1997，156：1969-1977.
14. Kotecha S，Mildner RJ，Prince LR，et al.The role of neutrophil apoptosis in the resolution of acute lung injury in newborn infants.Thorax，2003，58：961-967.
15. Nwakoby JE，Reddy K，Patel P，et al.Fas-mediated apoptosis of neutrophils in sera of patients with infection.Infect Immunol，2001，69：3343-3349.
16. Dunican AL，Lenemoth SJ，Grutkoski P，et al.TNF alpha-induced suppression of PMN apoptosis is mediated through interleukin-8 production.Shock，2000，14：284-88.
17. Park WY，Goodman RB，Steinberg KP，et al.Cytokine balance in the lungs of patients with acute respiratory distress syndrome.Am J Respir Crit Care Med，2001，164：1896-1903.
18. Hu M，Lin X，Du Q，et al.Regulation of polymorphonuclear leukocyte apoptosis：role of lung endothelium-epithelium bilayer transmigration.Am J Physiol Lung Cell Mol Physiol，2005，288：L266-L274.
19. Nakamura M，Matute-Bello G，Liles WC，et al.Differential response of human lung epithelial cells to Fas-induced apoptosis.Am J Pathol，2004，164：1949-1958.
20. Albertine KH，Soulier MF，Wang Z，et al.Fas and Fas ligand are up-regulated in pulmonary edema fluid and lung tissue of patients with acute lung injury and the acute respiratory distress syndrome.Am J Pathol，2002，161：1783-1796.
21. Matute-Bello G，Liles WC，F(xiàn)revert CW，et al.Recombinant human Fas ligand induces alveolar epithelial cell apoptosis and lung injury in rabbits.Am J Physiol Lung Cell Mol Physiol，2001，281：L328-L335.
22. Neff TA，Guo RF，Neff SB，et al.Relationship of acute lung inflammatory injury to Fas/FasL system.Am J Pathol，2005，166：685-694.
23. Kinoshita M，Ono S，Mochizuki H.Neutrophils mediate acute lung injury in rabbits：role of neutrophil elastase.Eur Surg Res，2000，32：337-346.
24. Wortinger MA，F(xiàn)oley JW，Larocque P，et al.Fas ligand-induced murine pulmonary inflammation is reduced by a stable decoy receptor 3 analogue.Immunology，2003，110：225-233.
25. Wang R，Zagariya A，Ang E，et al.Fas-induced apoptosis of alveolar epithelial cells requires ANG II generation and receptor interaction.Am J Physiol，1999，277：L1245-L1250.
26. Hagimoto N，Kuwano K，Inoshima I，et al.TGF-beta 1 as an enhancer of Fas-mediated apoptosis of lung epithelial cells.J Immunol，2002，168：6470-6478.
27. Vazquez de Lara L，Becerril C，Montano M，et al.Surfactant components modulate fibroblast apoptosis and type I collagen and collagenase-1 expression.Am J Physiol Lung Cell Mol Physiol，2000，279：L950-L957.
28. White MK，Baireddy V，Strayer DS.Natural protection from apoptosis by surfactant protein A in type II pneumocytes.Exp Cell Res，2001，263：183-192.
29. Scaffidi C，Schmitz I，Krammer PH，et al.The role of c-FLIP in modulation of CD95-induced apoptosis.J Biol Chem，1999，274：1541-1548.
30. Puneet P，Moochhala S，Bhatia M.Chemokines in acute respiratory distress syndrome Am J Physiol Lung Cell Mol Physiol，2005，288：L3-L15.
31. Chen JJ，Sun Y，Nabel GJ.Regulation of the proinflammatory effects of Fas ligand (CD95L).Science，1998，282：1714-1717.
32. Faouzi S，Burckhardt BE，Hanson JC，et al.Anti-Fas induces hepatic chemokines and promotes inflammation by an NF-kappa B-independent，caspase-3-dependent pathway.J Biol Chem，2001，276：49077-49082.
33. Yamaoka-Tojo M，Yamaguchi S，Nitobe J，et al.Dual response to Fas ligation in human endothelial cells：apoptosis and induction of chemokines，interleukin-8 and monocyte chemoattractant protein-1.Coron Artery Dis，2003，14：89-94.
  1. 1. Ware LB，Matthay MA.The acute respiratory distress syndrome.N Engl J Med，2000，342：1334-1349.
  2. 2. Matute-Bello G，Winn RK，Jonas M，et al.Fas (CD95) induces alveolar epithelial cell apoptosis in vivo：implications for acute pulmonary inflammation.Am J Pathol，2001，158：153-161.
  3. 3. Kitamura Y，Hashimoto S，Mizuta N，et al.Fas/FasL-dependent apoptosis of alveolar cells after lipopolysaccharide-induced lung injury in mice.Am J Respir Crit Care Med，2001，163：762-769.
  4. 4. Perl M，Chung CS，Ayala A.Apoptosis.Crit Care Med，2005，33：S526-S529.
  5. 5. French LE，Tschopp J.Protein-based therapeutic approaches targeting death receptors.Cell Death Differ，2003，10：117-123.
  6. 6. Wajant H.Death receptors.Essays Biochem，2003，39：53-71.
  7. 7. Suda T，Takahashi T，Golstein P，et al.Molecular cloning and expression of the Fas ligand，a novel member of the tumor necrosis factor family.Cell，1993，75：1169-1178.
  8. 8. Itoh N，Yonehara S，Ishii A，et al.The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis，Cell，1991，66：233-243.
  9. 9. Peter ME，Krammer PH.The CD95 (APO-1/Fas) DISC and beyond.Cell Death Differ，2003，10：26-35.
  10. 10. Scaffidi C，F(xiàn)ulda S，Srinivasan A，et al.Two CD95 (APO-1/Fas) signaling pathways.EMBO J，1998，17：1675-1687.
  11. 11. Korsmeyer SJ，Wei MC，Saito M，et al.Pro-apoptotic cascade activates BID，which oligomerizes BAK or BAX into pores that result in the release of cytochrome c.Cell Death Differ，2000，7：1166-1173.
  12. 12. Jimenez MF，Watson RW，Parodo J，et al.Dysregulated expression of neutrophil apoptosis in the systemic inflammatory response syndrome.Arch Surg，1997，132：1263-1269.
  13. 13. Matute-Bello G，Liles WC，Radella F 2nd，et al.Neutrophil apoptosis in the acute respiratory distress syndrome.Am J Respir Crit Care Med，1997，156：1969-1977.
  14. 14. Kotecha S，Mildner RJ，Prince LR，et al.The role of neutrophil apoptosis in the resolution of acute lung injury in newborn infants.Thorax，2003，58：961-967.
  15. 15. Nwakoby JE，Reddy K，Patel P，et al.Fas-mediated apoptosis of neutrophils in sera of patients with infection.Infect Immunol，2001，69：3343-3349.
  16. 16. Dunican AL，Lenemoth SJ，Grutkoski P，et al.TNF alpha-induced suppression of PMN apoptosis is mediated through interleukin-8 production.Shock，2000，14：284-88.
  17. 17. Park WY，Goodman RB，Steinberg KP，et al.Cytokine balance in the lungs of patients with acute respiratory distress syndrome.Am J Respir Crit Care Med，2001，164：1896-1903.
  18. 18. Hu M，Lin X，Du Q，et al.Regulation of polymorphonuclear leukocyte apoptosis：role of lung endothelium-epithelium bilayer transmigration.Am J Physiol Lung Cell Mol Physiol，2005，288：L266-L274.
  19. 19. Nakamura M，Matute-Bello G，Liles WC，et al.Differential response of human lung epithelial cells to Fas-induced apoptosis.Am J Pathol，2004，164：1949-1958.
  20. 20. Albertine KH，Soulier MF，Wang Z，et al.Fas and Fas ligand are up-regulated in pulmonary edema fluid and lung tissue of patients with acute lung injury and the acute respiratory distress syndrome.Am J Pathol，2002，161：1783-1796.
  21. 21. Matute-Bello G，Liles WC，F(xiàn)revert CW，et al.Recombinant human Fas ligand induces alveolar epithelial cell apoptosis and lung injury in rabbits.Am J Physiol Lung Cell Mol Physiol，2001，281：L328-L335.
  22. 22. Neff TA，Guo RF，Neff SB，et al.Relationship of acute lung inflammatory injury to Fas/FasL system.Am J Pathol，2005，166：685-694.
  23. 23. Kinoshita M，Ono S，Mochizuki H.Neutrophils mediate acute lung injury in rabbits：role of neutrophil elastase.Eur Surg Res，2000，32：337-346.
  24. 24. Wortinger MA，F(xiàn)oley JW，Larocque P，et al.Fas ligand-induced murine pulmonary inflammation is reduced by a stable decoy receptor 3 analogue.Immunology，2003，110：225-233.
  25. 25. Wang R，Zagariya A，Ang E，et al.Fas-induced apoptosis of alveolar epithelial cells requires ANG II generation and receptor interaction.Am J Physiol，1999，277：L1245-L1250.
  26. 26. Hagimoto N，Kuwano K，Inoshima I，et al.TGF-beta 1 as an enhancer of Fas-mediated apoptosis of lung epithelial cells.J Immunol，2002，168：6470-6478.
  27. 27. Vazquez de Lara L，Becerril C，Montano M，et al.Surfactant components modulate fibroblast apoptosis and type I collagen and collagenase-1 expression.Am J Physiol Lung Cell Mol Physiol，2000，279：L950-L957.
  28. 28. White MK，Baireddy V，Strayer DS.Natural protection from apoptosis by surfactant protein A in type II pneumocytes.Exp Cell Res，2001，263：183-192.
  29. 29. Scaffidi C，Schmitz I，Krammer PH，et al.The role of c-FLIP in modulation of CD95-induced apoptosis.J Biol Chem，1999，274：1541-1548.
  30. 30. Puneet P，Moochhala S，Bhatia M.Chemokines in acute respiratory distress syndrome Am J Physiol Lung Cell Mol Physiol，2005，288：L3-L15.
  31. 31. Chen JJ，Sun Y，Nabel GJ.Regulation of the proinflammatory effects of Fas ligand (CD95L).Science，1998，282：1714-1717.
  32. 32. Faouzi S，Burckhardt BE，Hanson JC，et al.Anti-Fas induces hepatic chemokines and promotes inflammation by an NF-kappa B-independent，caspase-3-dependent pathway.J Biol Chem，2001，276：49077-49082.
  33. 33. Yamaoka-Tojo M，Yamaguchi S，Nitobe J，et al.Dual response to Fas ligation in human endothelial cells：apoptosis and induction of chemokines，interleukin-8 and monocyte chemoattractant protein-1.Coron Artery Dis，2003，14：89-94.