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20 - Apoptosis in the Physiology and Diseases of the Respiratory Tract

from Part II - Cell Death in Tissues and Organs

Published online by Cambridge University Press:  07 September 2011

Douglas R. Green
By
Christian Taube  and
Martin Schuler
Edited by
John C. Reed
Douglas R. Green
Affiliation:
St. Jude Children's Research Hospital, Memphis, Tennessee
Christian Taube
Affiliation:
Johannes Gutenberg University Hospital
Martin Schuler
Affiliation:
West German Cancer Center
John C. Reed
Affiliation:
Sanford-Burnham Medical Research Institute, La Jolla, California
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Summary

The lung provides a huge contact interface between the organism and its environment. Its mucosal surfaces must permit gas exchange between the blood and air, but also act as a barrier against a plethora of microorganisms. In addition, inhaled toxins and particles may enter the organism via the lung. Accordingly, inflammatory airway and lung diseases are among the most prevalent human morbidities. Lung cancer, which in most cases can be attributed to tobacco smoking, is the leading cause of cancer-related mortality in the developed world. In this chapter, we summarize the role of apoptotic cell death in lung development and in clinical disease states.

Type
Chapter
Information
Apoptosis
Physiology and Pathology
 , pp. 221 - 230
Publisher: Cambridge University Press
Print publication year: 2011

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References

ATS/ERS (2002). American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med. 165, 277–304.
Albertine, K.H., Soulier, M.F., Wang, Z., Ishizaka, A., Hashimoto, S., Zimmerman, G.A., Matthay, M.A., and Ware, L.B. (2002). 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. 161, 1783–96.
Aoshiba, K., Yokohori, N., and Nagai, A. (2003). Alveolar wall apoptosis causes lung destruction and emphysematous changes. Am J Respir Cell Mol Biol. 28, 555–62.
Apolinario, R.M., Van Der Valk, P., de Jong, J.S., Deville, W., van Ark-Otte, J., Dingemans, A.-M.C., van Mourik, J.C., Postmus, P.E., Pinedo, H.M., and Giaccone, G. (1997). Prognostic value of the expression of p53, bcl-2, and bax oncoproteins, and neovascularization in patients with radically resected non-small cell lung cancer. J Clin Oncol. 15, 2456–66.
Ashkenazi, A., Pai, R.C., Fong, S., Leung, S., Lawrence, D.A., Marsters, S.A., Blackie, C., Chang, L., McMurtrey, A.E., Hebert, A., DeForge, L., Koumenis, I.L., Lewis, D., Harris, L., Koeppen, H., Shahrokh, Z., and Schwall, R.H. (1999). Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest. 104, 155–62.
Barbas-Filho, J.V., Ferreira, M.A., Sesso, A., Kairalla, R.A., Carvalho, C.R., and Capelozzi, V.L. (2001). Evidence of type II pneumocyte apoptosis in the pathogenesis of idiopathic pulmonary fibrosis (IFP)/usual interstitial pneumonia (UIP). J Clin Pathol. 54, 132–8.
Barnes, P.J., Shapiro, S.D., and Pauwels, R.A. (2003). Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J. 22, 672–88.
Beer, D.G., Kardia, S.L.R., Huang, C.-C., Giordano, T.J., Levin, A.M., Misek, D.E., Lin, L., Gharib, T.G., Thomas, D.G., Lizyness, M.L., Kuick, R., Hayasaka, S., Taylor, J.M.G., Iannettoni, M.D., Orringer, M.B., and Hanash, S. (2002). Gene-expression profiles predict survial of patients with lung adenocarcinoma. Nat Med. 8, 816–824.
Besse, B., Candé, C., Spano, J.P., Martin, A., Khayat, D., Le Chevalier, T., Tursz, T., Sabatier, L., Soria, J.C., and Kroemer, G. (2004). Nuclear localization of apoptosis protease activating factor-1 predicts survival after tumor resection in early-stage non-small cell lung cancer. Clin Cancer Res. 10, 5665–9.
Bruce, M.C., Honaker, C.E., and Cross, R.J. (1999). Lung fibroblasts undergo apoptosis following alveolarization. Am J Respir Cell Mol Biol. 20, 228–36.
Bull, T.M., Coldren, C.D., Geraci, M.W., and Voelkel, N.F. (2007). Gene expression profiling in pulmonary hypertension. Proc Am Thorac Soc. 4, 117–20.
Bykov, V.J.N., Issaeva, N., Shilov, A., Multcrantz, M., Pugacheva, E., Chumakov, P., Bergman, J., Wiman, K.G., and Selivanova, G. (2002). Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat Med. 8, 282–8.
Calabrese, F., Giacometti, C., Beghe, B., Rea, F., Loy, M., Zuin, R., Marulli, G., Baraldo, S., Saetta, M., and Valente, M. (2005). Marked alveolar apoptosis/proliferation imbalance in end-stage emphysema. Respir Res. 6:14., 14.
Checinska, A., Hoogeland, B.S., Rodriguez, J.A., Giaccone, G., and Kruyt, F.A. (2007). Role of XIAP in inhibiting cisplatin-induced caspase activation in non-small cell lung cancer cells: a small molecule Smac mimic sensitizes for chemotherapy-induced apoptosis by enhancing caspase-3 activation. Exp Cell Res. 313, 1215–24.
Chipuk, J.E., Maurer, U., Green, D.R., and Schuler, M. (2003). Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription. Cancer Cell 4, 371–381.
Cvetanovic, M., Mitchell, J.E., Patel, V., Avner, B.S., Su, Y., Van Der Saag, P.T., Witte, P.L., Fiore, S., Levine, J.S., and Ucker, D.S. (2006). Specific recognition of apoptotic cells reveals a ubiquitous and unconventional innate immunity. J Biol Chem. 281, 20055–67.
De Paepe, M.E., Johnson, B.D., Papadakis, K., and Luks, F.I. (1999a). Lung growth response after tracheal occlusion in fetal rabbits is gestational age-dependent. Am J Respir Cell Mol Biol. 21, 65–76.
De Paepe, M.E., Johnson, B.D., Papadakis, K., Sueishi, K., and Luks, F.I. (1998). Temporal pattern of accelerated lung growth after tracheal occlusion in the fetal rabbit. Am J Pathol. 152, 179–90.
De Paepe, M.E., Mao, Q., Chao, Y., Powell, J.L., Rubin, L.P., and Sharma, S. (2005). Hyperoxia-induced apoptosis and Fas/FasL expression in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol. 289, L647–59.
De Paepe, M.E., Sardesai, M.P., Johnson, B.D., Lesieur-Brooks, A.M., Papadakis, K., and Luks, F.I. (1999b). The role of apoptosis in normal and accelerated lung development in fetal rabbits. J Pediatr Surg. 34, 863–70.
Del Riccio, V., van Tuyl, M., and Post, M. (2004). Apoptosis in lung development and neonatal lung injury. Pediatr Res. 55, 183–9.
Droemann, D., Aries, S.P., Hansen, F., Moellers, M., Braun, J., Katus, H.A., and Dalhoff, K. (2000). Decreased apoptosis and increased activation of alveolar neutrophils in bacterial pneumonia. Chest. 117, 1679–84.
Fadok, V.A., Bratton, D.L., Konowal, A., Freed, P.W., Westcott, J.Y., and Henson, P.M. (1998). Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest. 101, 890–8.
Fedorov, L.M., Tyrsin, O.Y., Papadopoulos, T., Camarero, G., Götz, R., and Rapp, U.R. (2002). Bcl-2 determines susceptibility to induction of lung cancer by oncogenic C-Raf. Cancer Res. 62, 6297–303.
Fujita, M., Kuwano, K., Kunitake, R., Hagimoto, N., Miyazaki, H., Kaneko, Y., Kawasaki, M., Maeyama, T., and Hara, N. (1998). Endothelial cell apoptosis in lipopolysaccharide-induced lung injury in mice. Int Arch Allergy Immunol. 117, 202–8.
Galie, N., Hoeper, M.M., Humbert, M., Torbicki, A., Vachiery, J-L., Barbera, J.A., Beghetti, M., Corris, P., Gaine, S., Gibbs, J.S., Gomez-Sanchez, M.A., Jondeau, G., Klepetko, W., Opitz, C., Peacock, A., Rubin, L., Zellweger, M., and Simonneau, G. (2009). Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J; 34: 1219–1263.
Greco, F.A., Bonomi, P., Crawford, J., Kelly, K., Oh, Y., Halpern, W., Lo, L., Gallant, G., and Klein, J. (2008). Phase 2 study of mapatumumab, a fully human agonistic monoclonal antibody which targets and activates the TRAIL receptor-1, in patients with advanced non-small cell lung cancer. Lung Cancer. 61, 82–90.
Hagimoto, N., Kuwano, K., Miyazaki, H., Kunitake, R., Fujita, M., Kawasaki, M., Kaneko, Y., and Hara, N. (1997). Induction of apoptosis and pulmonary fibrosis in mice in response to ligation of Fas antigen. Am J Respir Cell Mol Biol. 17, 272–8.
Hargitai, B., Szabo, V., Hajdu, J., Harmath, A., Pataki, M., Farid, P., Papp, Z., and Szende, B. (2001). Apoptosis in various organs of preterm infants: histopathologic study of lung, kidney, liver, and brain of ventilated infants. Pediatr Res. 50, 110–14.
Hodge, S., Hodge, G., Ahern, J., Jersmann, H., Holmes, M., and Reynolds, P.N. (2007). Smoking alters alveolar macrophage recognition and phagocytic ability: implications in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 37, 748–55.
Hodge, S., Hodge, G., Holmes, M., and Reynolds, P.N. (2005). Increased airway epithelial and T-cell apoptosis in COPD remains despite smoking cessation. Eur Respir J. 25, 447–54.
Hodge, S., Hodge, G., Nairn, J., Holmes, M., and Reynolds, P.N. (2006). Increased airway granzyme B and perforin in current and ex-smoking COPD subjects. COPD. 3, 179–87.
Hoffarth, S., Zitzer, A., Wiewrodt, R., Hähnel, P.S., Beyer, V., Kreft, A., Biesterfeld, S., and Schuler, M. (2008). pp32/PHAPI determines the apoptosis response of non-small-cell lung cancer. Cell Death Differ. 15, 170.
Holopainen, R., Aho, H., Laine, J., Peuravuori, H., Soukka, H., and Kaapa, P. (1999). Human meconium has high phospholipase A2 activity and induces cellular injury and apoptosis in piglet lungs. Pediatr Res. 46, 626–32.
Huynh, M.L., Fadok, V.A., and Henson, P.M. (2002). Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J Clin Invest. 109, 41–50.
Imai, K., Mercer, B.A., Schulman, L.L., Sonett, J.R., and D’Armiento, J.M. (2005). Correlation of lung surface area to apoptosis and proliferation in human emphysema. Eur Respir J. 25, 250–8.
Jiang, X., Kim, H.-E., Shu, H., Zhao, Y., Zhang, H., Kofron, J., Donnelly, J., Burns, D., Ng, S.-C., Rosenberg, S., and Wang, X. (2003). Distinctive roles of PHAP proteins and prothymosin-a in a death regulatory pathway. Science. 299, 223–6.
Jin, H., Yang, R., Fong, S., Totpal, K., Lawrence, D., Zheng, Z., Ross, J., Koeppen, H., Schwall, R., and Ashkenazi, A. (2004). Apo2 Ligand/tumor necrosis factor-related apoptosis-inducing ligand cooperates with chemotherapy to inhibit orthopic lung tumor growth and improve survival. Cancer Res. 64, 4900–5.
Johnson, L., Mercer, K., Greenbaum, D., Bronson, R.T., Crowley, D., Tuveson, D.A., and Jacks, T. (2001). Somatic activation of the K- oncogene causes early onset lung cancer in mice. Nature. 410, 1111–16.
Johnstone, R.W., Ruefli, A.A., and Lowe, S.W. (2002). Apoptosis: a link between cancer genetics and chemotherapy. Cell. 108, 153–64.
Karrasch, S., Holz, O., and Jorres, R.A. (2008). Aging and induced senescence as factors in the pathogenesis of lung emphysema. Respir Med. 102, 1215–30.
Kasahara, Y., Tuder, R.M., Cool, C.D., Lynch, D.A., Flores, S.C., and Voelkel, N.F. (2001a). Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema. Am J Respir Crit Care Med. 163, 737–44.
Kasahara, Y., Tuder, R.M., Cool, C.D., Lynch, D.A., Flores, S.C., and Voelkel, N.F. (2001b). Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema. Am J Respir Crit Care Med. 163, 737–44.
Kasahara, Y., Tuder, R.M., Taraseviciene-Stewart, L., Le Cras, T.D., Abman, S., Hirth, P.K., Waltenberger, J., and Voelkel, N.F. (2000). Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest. 106, 1311–19.
Kawasaki, M., Kuwano, K., Hagimoto, N., Matsuba, T., Kunitake, R., Tanaka, T., Maeyama, T., and Hara, N. (2000). Protection from lethal apoptosis in lipopolysaccharide-induced acute lung injury in mice by a caspase inhibitor. Am J Pathol. 157, 597–603.
Kitamura, Y., Hashimoto, S., Mizuta, N., Kobayashi, A., Kooguchi, K., Fujiwara, I., and Nakajima, H. (2001). Fas/FasL-dependent apoptosis of alveolar cells after lipopolysaccharide-induced lung injury in mice. Am J Respir Crit Care Med. 163, 762–9.
Kresch, M.J., Christian, C., Wu, F., and Hussain, N. (1998). Ontogeny of apoptosis during lung development. Pediatr Res. 43, 426–31.
Kuwano, K., Hagimoto, N., Kawasaki, M., Yatomi, T., Nakamura, N., Nagata, S., Suda, T., Kunitake, R., Maeyama, T., Miyazaki, H., and Hara, N. (1999). Essential roles of the Fas-Fas ligand pathway in the development of pulmonary fibrosis. J Clin Invest. 104, 13–19.
Kuwano, K., Kunitake, R., Kawasaki, M., Nomoto, Y., Hagimoto, N., Nakanishi, Y., and Hara, N. (1996). P21Waf1/Cip1/Sdi1 and p53 expression in association with DNA strand breaks in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 154, 477–83.
Kuwano, K., Kunitake, R., Maeyama, T., Hagimoto, N., Kawasaki, M., Matsuba, T., Yoshimi, M., Inoshima, I., Yoshida, K., and Hara, N. (2001). Attenuation of bleomycin-induced pneumopathy in mice by a caspase inhibitor. Am J Physiol Lung Cell Mol Physiol. 280, L316–25.
Lane, K.B., Machado, R.D., Pauciulo, M.W., Thomson, J.R., Phillips, J.A., III, Loyd, J.E., Nichols, W.C., and Trembath, R.C. (2000). Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Nat Genet. 26, 81–4.
Lee, C.G., Cho, S.J., Kang, M.J., Chapoval, S.P., Lee, P.J., Noble, P.W., Yehualaeshet, T., Lu, B., Flavell, R.A., Milbrandt, J., Homer, R.J., and Elias, J.A. (2004). Early growth response gene 1-mediated apoptosis is essential for transforming growth factor beta1-induced pulmonary fibrosis. J Exp Med. 200, 377–89.
Levesque, B.M., Vosatka, R.J., and Nielsen, H.C. (2000). Dihydrotestosterone stimulates branching morphogenesis, cell proliferation, and programmed cell death in mouse embryonic lung explants. Pediatr Res. 47, 481–91.
Lu, Q., Xu, D.Z., Davidson, M.T., Hasko, G., and Deitch, E.A. (2004). Hemorrhagic shock induces endothelial cell apoptosis, which is mediated by factors contained in mesenteric lymph. Crit Care Med. 32, 2464–70.
Lukkarinen, H.P., Laine, J., and Kaapa, P.O. (2003). Lung epithelial cells undergo apoptosis in neonatal respiratory distress syndrome. Pediatr Res. 53, 254–9.
Mantell, L.L., Horowitz, S., Davis, J.M., and Kazzaz, J.A. (1999). Hyperoxia-induced cell death in the lung–the correlation of apoptosis, necrosis, and inflammation. Ann N Y Acad Sci. 887, 171–80.
Martin, T.R., Hagimoto, N., Nakamura, M., and Matute-Bello, G. (2005). Apoptosis and epithelial injury in the lungs. Proc Am Thorac Soc. 2, 214–20.
Matute-Bello, G., Liles, W.C., Frevert, C.W., Nakamura, M., Ballman, K., Vathanaprida, C., Kiener, P.A., and Martin, T.R. (2001). Recombinant human Fas ligand induces alveolar epithelial cell apoptosis and lung injury in rabbits. Am J Physiol Lung Cell Mol Physiol. 281, L328–35.
Matute-Bello, G., Liles, W.C., Radella, F., Steinberg, K.P., Ruzinski, J.T., Jonas, M., Chi, E.Y., Hudson, L.D., and Martin, T.R. (1997). Neutrophil apoptosis in the acute respiratory distress syndrome. Am J Respir Crit Care Med. 156, 1969–77.
Matute-Bello, G., Liles, W.C., Steinberg, K.P., Kiener, P.A., Mongovin, S., Chi, E.Y., Jonas, M., and Martin, T.R. (1999). Soluble Fas ligand induces epithelial cell apoptosis in humans with acute lung injury (ARDS). J Immunol. 163, 2217–25.
May, M., Strobel, P., Preisshofen, T., Seidenspinner, S., Marx, A., and Speer, C.P. (2004). Apoptosis and proliferation in lungs of ventilated and oxygen-treated preterm infants. Eur Respir J. 23, 113–21.
McDonnell, T.J., Fang, B., Yu, R., Kagawa, S., Hunt, K.K., McDonnell, T.J., Roth, J.A., and Swisher, S.G. (2000). Adenoviral Bak overexpression mediates caspase-dependent tumor killing. Cancer Res. 60, 788–92.
McMurtry, M.S., Archer, S.L., Altieri, D.C., Bonnet, S., Haromy, A., Harry, G., Bonnet, S., Puttagunta, L., and Michelakis, E.D. (2005). Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension. J Clin Invest. 115, 1479–91.
Metzger, R.J., Klein, O.D., Martin, G.R., and Krasnow, M.A. (2008). The branching programme of mouse lung development. Nature. 453, 745–50.
Morrell, N.W., Yang, X., Upton, P.D., Jourdan, K.B., Morgan, N., Sheares, K.K., and Trembath, R.C. (2001). Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-beta(1) and bone morphogenetic proteins. Circulation. 104, 790–5.
Nakamura, M., Matute-Bello, G., Liles, W.C., Hayashi, S., Kajikawa, O., Lin, S.M., Frevert, C.W., and Martin, T.R. (2004). Differential response of human lung epithelial cells to fas-induced apoptosis. Am J Pathol. 164, 1949–58.
Oltersdorf, T., Elmore, S.W., Shoemaker, A.R., Armstrong, R.C., Augeri, D.J., Belli, B.A., Bruncko, M., Deckwerth, T.L., Dinges, J., Hajduk, P.J., Joseph, M.K., Kitada, S., Korsmeyer, S.J., Kunzer, A.R., Letai, A., Li, C., Mitten, M.J., Nettesheim, D.G., Ng, S., Nimmer, P.M., O’Connor, J.M., Oleksijew, A., Petros, A.M., Reed, J.C., Shen, W., Tahir, S.K., Thompson, C.B., Tomaselli, K.J., Wang, B., Wendt, M.D., Zhang, H., Fesik, S.W., and Rosenberg, S.H. (2005). An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 435, 677–81.
Petrache, I., Natarajan, V., Zhen, L., Medler, T.R., Richter, A.T., Cho, C., Hubbard, W.C., Berdyshev, E.V., and Tuder, R.M. (2005). Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice. Nat Med. 11, 491–8.
Plataki, M., Koutsopoulos, A.V., Darivianaki, K., Delides, G., Siafakas, N.M., and Bouros, D. (2005). Expression of apoptotic and antiapoptotic markers in epithelial cells in idiopathic pulmonary fibrosis. Chest. 127, 266–74.
Potti, A., Mukherjee, S., Petersen, R., Dressman, H.K., Bild, A., Koontz, J., Kratzke, R., Watson, M.A., Kelley, M., Ginsburg, G.S., West, M., Harpole, D.H., and Nevins, J.R. (2006). A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. N Engl J Med. 355, 570–80.
Rabe, K.F., Hurd, S., Anzueto, A., Barnes, P.J., Buist, S.A., Calverley, P., Fukuchi, Y., Jenkins, C., Rodriguez-Roisin, R., Van, W.C., and Zielinski, J. (2007). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 176, 532–55.
Rabinovitch, M. (2008). Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest. 118, 2372–9.
Radetzki, S., Köhne, C.H., von Haefen, C., Gillisen, B., Sturm, I., Dörken, B., and Daniel, P.T. (2002). The apoptosis promoting Bcl-2 homologues Bak and Nbk/Bik overcome drug resistance in Mdr-1-negative and Mdr-1-overexpressing breast cancer cell lines. Oncogene. 21, 227–38.
Ranger, A.M., Malynn, B.A., and Korsmeyer, S.J. (2001). Mouse models of cell death. Nat Genet. 28, 113–18.
Roth, J.A., Nguyen, D., Lawrence, D.D., Kemp, B.L., Carrasco, C.H., Ferson, D.Z., Hong, W.K., Komaki, R., Lee, J.J., Nesbitt, J.C., Pisters, K.M.W., Putnam, J.B., Schea, R., Shin, D.M., Walsh, G.L., Dolormente, M.M., Han, C.-I., Martin, F.D., Yen, N., Xu, K., Stephens, L.C., McDonnell, T.J., Mukhopadhyay, T., and Cai, D. (1996). Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer. Nat Med. 2, 985–91.
Scavo, L.M., Ertsey, R., Chapin, C.J., Allen, L., and Kitterman, J.A. (1998). Apoptosis in the development of rat and human fetal lungs. Am J Respir Cell Mol Biol. 18, 21–31.
Schittny, J.C., Djonov, V., Fine, A., and Burri, P.H. (1998). Programmed cell death contributes to postnatal lung development. Am J Respir Cell Mol Biol. 18, 786–93.
Segura-Valdez, L., Pardo, A., Gaxiola, M., Uhal, B.D., Becerril, C., and Selman, M. (2000). Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD. Chest. 117, 684–94.
Shapiro, S.D. (2003). Proteolysis in the lung. Eur Respir J Suppl. 44, 30s–2s.
Sordella, R., Bell, D.W., Haber, D.A., and Settleman, J. (2004). Gefitinib-sensitizing mutations in lung cancer activate anti-apoptotic pathways. Science 305, 1163–7.
Sweet-Cordereo, A., Mukherjee, S., Subramanian, A., You, H., Roix, J.J., Ladd-Acosta, C., Mesirov, J., Golub, T.R., and Jacks, T. (2005). An oncogenic expression signature identified by cross-species gene-expression analysis. Nat Genet. 37, 48–55.
Takata, T., Tanaka, F., Yamada, T., Yanagihara, K., Otake, Y., Kawano, Y., Nakagawa, T., Miyahara, R., Oyanagi, H., Inui, K., and Wada, H. (2001). Clinical significance of caspase-3 expression in pathologic-stage I, nonsmall-cell lung cancer. Int J Cancer. 96, 54–60.
Tang, K., Rossiter, H.B., Wagner, P.D., and Breen, E.C. (2004). Lung-targeted VEGF inactivation leads to an emphysema phenotype in mice. J Appl Physiol. 97, 1559–66.
Thannickal, V.J. and Horowitz, J.C. (2006). Evolving concepts of apoptosis in idiopathic pulmonary fibrosis. Proc Am Thorac Soc. 3, 350–6.
Tse, C., Shoemaker, A.R., Adickes, J., Anderson, M.G., Chen, J., Jin, S., Johnson, E.F., Marsh, K.C., Mitten, M.J., Nimmer, P., Roberts, L., Tahir, S.K., Xiao, Y., Yang, X., Zhang, H., Fesik, S., Rosenberg, S.H., and Elmore, S.W. (2008). ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 68, 3421–8.
Tuder, R.M., Zhen, L., Cho, C.Y., Taraseviciene-Stewart, L., Kasahara, Y., Salvemini, D., Voelkel, N.F., and Flores, S.C. (2003). Oxidative stress and apoptosis interact and cause emphysema due to vascular endothelial growth factor receptor blockade. Am J Respir Cell Mol Biol. 29, 88–97.
Uhal, B.D., Joshi, I., Hughes, W.F., Ramos, C., Pardo, A., and Selman, M. (1998). Alveolar epithelial cell death adjacent to underlying myofibroblasts in advanced fibrotic human lung. Am J Physiol. 275, L1192–9.
Vandivier, R.W., Fadok, V.A., Hoffmann, P.R., Bratton, D.L., Penvari, C., Brown, K.K., Brain, J.D., Accurso, F.J., and Henson, P.M. (2002). Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis. J Clin Invest. 109, 661–70.
Varfolomeev, E., Blankenship, J.W., Wayson, S.M., Fedorova, A.V., Kayagaki, N., Garg, P., Zobel, K., Dynek, J.N., Elliott, L.O., Wallweber, H.J., Flygare, J.A., Fairbrother, W.J., Deshayes, K., Dixit, V.M., and Vucic, D. (2007). IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell, 131, 669–81.
Ventura, A., Young, A.F., Winslow, M.M., Lintault, L., Meissner, A., Erkeland, S.J., Newman, J., Bronson, R.T., Crowley, D., Stone, J.R., Jaenisch, R., Sharp, P.A., and Jacks, T. (2008). Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell. 132, 875–86.
Walczak, H., Miller, R.E., Ariail, K., Gliniak, B., Griffith, T.S., Kubin, M., Chin, W., Jones, J., Woodward, A., Le, T., Smith, C., Smolak, P., Goodwin, R.G., Rauch, C.T., Schuh, J.C.L., and Lynch, D.H. (1999). Tumoricidal activity of tumor necrosis factor related apoptosis inducing ligand in vivo. Nat Med. 5, 157–63.
Wallach-Dayan, S.B., Izbicki, G., Cohen, P.Y., Gerstl-Golan, R., Fine, A., and Breuer, R. (2006). Bleomycin initiates apoptosis of lung epithelial cells by ROS but not by Fas/FasL pathway. Am J Physiol Lung Cell Mol Physiol. 290, L790–6.
Wang, H.C., Shun, C.T., Hsu, S.M., Kuo, S.H., Luh, K.T., and Yang, P.C. (2002). Fas/Fas ligand pathway is involved in the resolution of type II pneumocyte hyperplasia after acute lung injury: evidence from a rat model. Crit Care Med. 30, 1528–34.
Wang, R., Ibarra-Sunga, O., Verlinski, L., Pick, R., and Uhal, B.D. (2000). Abrogation of bleomycin-induced epithelial apoptosis and lung fibrosis by captopril or by a caspase inhibitor. Am J Physiol Lung Cell Mol Physiol. 279, L143–51.
Wang, R., Ramos, C., Joshi, I., Zagariya, A., Pardo, A., Selman, M., and Uhal, B.D. (1999). Human lung myofibroblast-derived inducers of alveolar epithelial apoptosis identified as angiotensin peptides. Am J Physiol. 277, L1158–64.
Wesarg, E., Hoffarth, S., Wiewrodt, R., Kröll, M., Biesterfeld, S., Huber, C., and Schuler, M. (2007). Targeting BCL-2 family proteins to overcome drug resistance in non-small cell lung cancer. Int J Cancer. 121, 2387–94.
Yang, L., Mashima, T., Sato, S., Mochizuki, M., Sakamoto, H., Yamori, T., Oh-Hara, T., and Tsuruo, T. (2003). Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic effect of a novel polyarginine-conjugated Smac peptide. Cancer Res. 63, 831–7.
Yokohori, N., Aoshiba, K., and Nagai, A. (2004). Increased levels of cell death and proliferation in alveolar wall cells in patients with pulmonary emphysema. Chest. 125, 626–32.
Zagariya, A., Bhat, R., Chari, G., Uhal, B., Navale, S., and Vidyasagar, D. (2005). Apoptosis of airway epithelial cells in response to meconium. Life Sci. 76, 1849–58.
Zhang, W.W., Fang, X., Mazur, W., French, B.A., Georges, R.N., and Roth, J.A. (1994). High-efficiency gene transfer and high-level expression of wild- type p53 in human lung cancer cells mediated by recombinant adenovirus. Cancer Gene Ther. 1, 5–13.
Zheng, T., Kang, M.J., Crothers, K., Zhu, Z., Liu, W., Lee, C.G., Rabach, L.A., Chapman, H.A., Homer, R.J., Aldous, D., De Sanctis, G.T., Underwood, S., Graupe, M., Flavell, R.A., Schmidt, J.A., and Elias, J.A. (2005). Role of cathepsin S-dependent epithelial cell apoptosis in IFN-gamma-induced alveolar remodeling and pulmonary emphysema. J Immunol. 174, 8106–15.

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