title: Acute lung injury: apoptosis in effector and target cells of the upper and lower airway compartment.
abstract: Apoptotic cell death has been considered an underlying mechanism in acute lung injury. To evaluate the evidence of this process, apoptosis rate was determined in effector cells (alveolar macrophages, neutrophils) and target cells (tracheobronchial and alveolar epithelial cells) of the respiratory compartment upon exposure to hypoxia and endotoxin stimulation in vitro. Cells were exposed to 5% oxygen or incubated with lipopolysaccharide (LPS) for 4, 8 and 24 h, and activity of caspase-3, -8 and -9 was determined. Caspase-3 of alveolar macrophages was increased at all three time-points upon LPS stimulation, while hypoxia did not affect apoptosis rate at early time-points. In neutrophils, apoptosis was decreased in an early phase of hypoxia at 4 h. However, enhanced expression of caspase-3 activity was seen at 8 and 24 h. In the presence of LPS a decreased apoptosis rate was observed at 8 h compared to controls, while it was increased at 24 h. Tracheobronchial as well as alveolar epithelial cells experienced an enhanced caspase-3 activity upon LPS stimulation with no change of apoptosis rate under hypoxia. While increased apoptosis rate is triggered through an intrinsic and extrinsic pathway in alveolar macrophages, intrinsic signalling is activated in tracheobronchial epithelial cells. The exact pathway pattern in neutrophils and alveolar epithelial cells could not be determined. These data clearly demonstrate that upon injury each cell type experiences its own apoptosis pattern. Further experiments need to be performed to determine the functional role of these apoptotic processes in acute lung injury.
authors.affiliation: Institute of Physiology and Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: B Roth
authors.initials: BR
authors.lastname: Z'graggen
authors.forename: J
authors.initials: J
authors.lastname: Tornic
authors.forename: B
authors.initials: B
authors.lastname: Müller-Edenborn
authors.forename: L
authors.initials: L
authors.lastname: Reyes
authors.forename: C
authors.initials: C
authors.lastname: Booy
authors.forename: B
authors.initials: B
authors.lastname: Beck-Schimmer
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001980:Bronchi / Q000166:cytology; D002166:Camptothecin / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D020545:Respiratory Mucosa / Q000166:cytology; D012137:Respiratory System / Q000166:cytology*; D013047:Specific Pathogen-Free Organisms; D014132:Trachea / Q000166:cytology
chemical_list: D008070:Lipopolysaccharides; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D002166:Camptothecin
references.citation: Blood. 1997 Nov 1;90(9):3356-63
references.pmid: 9345017
references.citation: Crit Care. 2003 Oct;7(5):355-8
references.pmid: 12974968
references.citation: Am J Respir Cell Mol Biol. 1998 Dec;19(6):867-74
references.pmid: 9843920
references.citation: N Engl J Med. 2000 May 4;342(18):1334-49
references.pmid: 10793167
references.citation: Am J Physiol Lung Cell Mol Physiol. 2006 Jan;290(1):L86-96
references.pmid: 16100285
references.citation: Monaldi Arch Chest Dis. 1998 Feb;53(1):56-63
references.pmid: 9632909
references.citation: Am J Respir Crit Care Med. 1998 Aug;158(2):675-9
references.pmid: 9700150
references.citation: Am J Respir Crit Care Med. 2003 Apr 1;167(7):1027-35
references.pmid: 12663342
references.citation: Pharmacol Res. 2009 Nov;60(5):418-28
references.pmid: 19467329
references.citation: Inflammation. 2005 Feb;29(1):55-63
references.pmid: 16502347
references.citation: Am Rev Respir Dis. 1990 Feb;141(2):471-501
references.pmid: 2405761
references.citation: In Vitro. 1974 Sep-Oct;10(3-4):230-7
references.pmid: 4616002
references.citation: Am J Physiol Lung Cell Mol Physiol. 2000 Mar;278(3):L572-9
references.pmid: 10710530
references.citation: Shock. 2008 Dec;30(6):628-33
references.pmid: 18520705
references.citation: Am J Physiol Lung Cell Mol Physiol. 2008 Apr;294(4):L632-41
references.pmid: 18203816
references.citation: Mol Cell. 2003 Feb;11(2):529-41
references.pmid: 12620239
references.citation: Mol Biol Rep. 2010 Oct;37(7):3051-6
references.pmid: 19823951
references.citation: Am J Respir Cell Mol Biol. 1996 Jul;15(1):64-70
references.pmid: 8679223
references.citation: J Immunol. 2000 Mar 1;164(5):2650-9
references.pmid: 10679105
references.citation: Nature. 2000 Oct 12;407(6805):770-6
references.pmid: 11048727
references.citation: Crit Care. 2006;10(6):R155
references.pmid: 17092345
references.citation: Monaldi Arch Chest Dis. 1999 Aug;54(4):345-9
references.pmid: 10546479
references.citation: Eur Respir J. 2009 Jun;33(6):1403-14
references.pmid: 19164355