Apoptosis and Epithelial Injury in the Lungs

Overview

Journal Proc Am Thorac Soc

Specialty Pulmonary Medicine

Date 2005 Oct 14

PMID 16222040

Citations 100

Authors

Thomas R Martin

Naoki Hagimoto

Morio Nakamura

Gustavo Matute-Bello

Affiliations

Soon will be listed here.

Abstract

Epithelial injury is a critical event in the development of acute lung injury, but the mechanisms that cause death of the alveolar epithelium are not completely understood. Epithelial death occurs by necrosis and apoptosis; more information is needed about the balance between these two types of cell death in the lungs. Direct epithelial necrosis probably occurs in response to bacterial exotoxins and over-distension of alveolar units by mechanical ventilation. Apoptosis is a regulated form of cell death that is mediated by membrane death receptors and direct mitochondrial injury. Apoptosis pathways are activated in the lungs of patients with acute lung injury, in part by activation of the membrane Fas death receptor by soluble Fas ligand (sFasL), which accumulates in biologically active form at the onset of lung injury. Accumulating evidence in humans and experimental models links sFasL and Fas pathway with lung epithelial injury and fibrosis. New strategies to inhibit Fas-mediated epithelial apoptosis need to be developed in order to develop new ways to preserve epithelial function in patients who develop acute lung injury.

Citing Articles

Cannabidiol protects lung against inflammation and apoptosis in a rat model of blunt chest trauma via Bax/Bcl-2/Cas-9 signaling pathway.

Emre A, Mehtap S, Cem D, Ilter I, Melih A, Ozlem O Eur J Trauma Emerg Surg. 2025; 51(1):95.

PMID: 39918746 PMC: 11805814. DOI: 10.1007/s00068-025-02767-0.

Matrix-free human lung organoids derived from induced pluripotent stem cells to model lung injury.

Budeus B, Kroepel C, Stasch L, Klein D Stem Cell Res Ther. 2024; 15(1):468.

PMID: 39696649 PMC: 11657174. DOI: 10.1186/s13287-024-04106-3.

Monocyte-Derived Macrophages Induce Alveolar Macrophages Death via TNF-α in Acute Lung Injury.

Xiao J, Hou F, Wang H, Wang R, Liu Y, Wu X Immun Inflamm Dis. 2024; 12(12):e70081.

PMID: 39660881 PMC: 11632899. DOI: 10.1002/iid3.70081.

Aging-Associated Molecular Changes in Human Alveolar Type I Cells.

Liu X, Zhang X, Liang J, Noble P, Jiang D J Respir Biol Transl Med. 2024; 1(3).

PMID: 39220636 PMC: 11361087. DOI: 10.35534/jrbtm.2024.10012.

Crtc1 deficiency protects against sepsis-associated acute lung injury through activating akt signaling pathway.

Chen M, Lv J, Guo N, Ji T, Fang Y, Wang Z J Inflamm (Lond). 2024; 21(1):12.

PMID: 38644501 PMC: 11034098. DOI: 10.1186/s12950-024-00385-y.

References

Matute-Bello G, Liles W, Steinberg K, Kiener P, Mongovin S, Chi E . Soluble Fas ligand induces epithelial cell apoptosis in humans with acute lung injury (ARDS). J Immunol. 1999; 163(4):2217-25. View

Hagimoto N, Kuwano K, Kawasaki M, Yoshimi M, Kaneko Y, Kunitake R . Induction of interleukin-8 secretion and apoptosis in bronchiolar epithelial cells by Fas ligation. Am J Respir Cell Mol Biol. 1999; 21(3):436-45. DOI: 10.1165/ajrcmb.21.3.3397. View

Konopleva M, Zhao S, Xie Z, Segall H, Younes A, Claxton D . Apoptosis. Molecules and mechanisms. Adv Exp Med Biol. 1999; 457:217-36. View

Chang M, Binder C, Miller Y, Subbanagounder G, Silverman G, Berliner J . Apoptotic cells with oxidation-specific epitopes are immunogenic and proinflammatory. J Exp Med. 2004; 200(11):1359-70. PMC: 2211955. DOI: 10.1084/jem.20031763. View

Lu Q, Xu D, Davidson M, Hasko G, Deitch E . Hemorrhagic shock induces endothelial cell apoptosis, which is mediated by factors contained in mesenteric lymph. Crit Care Med. 2004; 32(12):2464-70. DOI: 10.1097/01.ccm.0000147833.51214.03. View

Krick S, Eul B, Hanze J, Savai R, Grimminger F, Seeger W . Role of hypoxia-inducible factor-1alpha in hypoxia-induced apoptosis of primary alveolar epithelial type II cells. Am J Respir Cell Mol Biol. 2005; 32(5):395-403. DOI: 10.1165/rcmb.2004-0314OC. View

Strater J, Gunthert A, Bruderlein S, Moller P . Microwave irradiation of paraffin-embedded tissue sensitizes the TUNEL method for in situ detection of apoptotic cells. Histochem Cell Biol. 1995; 103(2):157-60. DOI: 10.1007/BF01454013. View

Barbas-Filho J, Ferreira M, Sesso A, Kairalla R, Carvalho C, Capelozzi V . Evidence of type II pneumocyte apoptosis in the pathogenesis of idiopathic pulmonary fibrosis (IFP)/usual interstitial pneumonia (UIP). J Clin Pathol. 2001; 54(2):132-8. PMC: 1731356. DOI: 10.1136/jcp.54.2.132. View

Fadok V, de Cathelineau A , Daleke D, Henson P, Bratton D . Loss of phospholipid asymmetry and surface exposure of phosphatidylserine is required for phagocytosis of apoptotic cells by macrophages and fibroblasts. J Biol Chem. 2000; 276(2):1071-7. DOI: 10.1074/jbc.M003649200. View

10.

Ware L, Matthay M . Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001; 163(6):1376-83. DOI: 10.1164/ajrccm.163.6.2004035. View

11.

Matute-Bello G, Liles W, Frevert C, Nakamura M, Ballman K, Vathanaprida C . Recombinant human Fas ligand induces alveolar epithelial cell apoptosis and lung injury in rabbits. Am J Physiol Lung Cell Mol Physiol. 2001; 281(2):L328-35. DOI: 10.1152/ajplung.2001.281.2.L328. View

12.

Matute-Bello G, Frevert C, Liles W, Nakamura M, Ruzinski J, Ballman K . Fas/Fas ligand system mediates epithelial injury, but not pulmonary host defenses, in response to inhaled bacteria. Infect Immun. 2001; 69(9):5768-76. PMC: 98694. DOI: 10.1128/IAI.69.9.5768-5776.2001. View

13.

Henson P, Bratton D, Fadok V . Apoptotic cell removal. Curr Biol. 2001; 11(19):R795-805. DOI: 10.1016/s0960-9822(01)00474-2. View

14.

Deveraux Q, Schendel S, Reed J . Antiapoptotic proteins. The bcl-2 and inhibitor of apoptosis protein families. Cardiol Clin. 2002; 19(1):57-74. DOI: 10.1016/s0733-8651(05)70195-8. View

15.

Bannerman D, Tupper J, Kelly J, Winn R, Harlan J . The Fas-associated death domain protein suppresses activation of NF-kappa B by LPS and IL-1 beta. J Clin Invest. 2002; 109(3):419-25. PMC: 150862. DOI: 10.1172/JCI14774. View

16.

Duckett C . Apoptosis and NF-kappa B: the FADD connection. J Clin Invest. 2002; 109(5):579-80. PMC: 150897. DOI: 10.1172/JCI15197. View

17.

Thome M, Tschopp J . Regulation of lymphocyte proliferation and death by FLIP. Nat Rev Immunol. 2002; 1(1):50-8. DOI: 10.1038/35095508. View

18.

Hagimoto N, Kuwano K, Inoshima I, Yoshimi M, Nakamura N, Fujita M . TGF-beta 1 as an enhancer of Fas-mediated apoptosis of lung epithelial cells. J Immunol. 2002; 168(12):6470-8. DOI: 10.4049/jimmunol.168.12.6470. View

19.

Cocca B, Cline A, Radic M . Blebs and apoptotic bodies are B cell autoantigens. J Immunol. 2002; 169(1):159-66. DOI: 10.4049/jimmunol.169.1.159. View

20.

Matthay M, Folkesson H, Clerici C . Lung epithelial fluid transport and the resolution of pulmonary edema. Physiol Rev. 2002; 82(3):569-600. DOI: 10.1152/physrev.00003.2002. View