Fas/FasL-mediated apoptosis in perinatal murine lungs
1 Program in Fetal Medicine, Departments of 2 Pathology and 4 Pediatrics, Women and Infants Hospital, Providence 02905; and Departments of 3 Pathology and Laboratory Medicine, 5 Pediatrics, and 6 Surgery, Brown Medical School, Providence, Rhode Island 02905 Submitted 1 April 2004 ; accepted in final...
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| Veröffentlicht in: | American journal of physiology. Lung cellular and molecular physiology 2004-10, Vol.287 (4), p.L730-L742 |
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| container_title | American journal of physiology. Lung cellular and molecular physiology |
| container_volume | 287 |
| creator | De Paepe, Monique E Mao, Quanfu Embree-Ku, Michelle Rubin, Lewis P Luks, Francois I |
| description | 1 Program in Fetal Medicine, Departments of 2 Pathology and 4 Pediatrics, Women and Infants Hospital, Providence 02905; and Departments of 3 Pathology and Laboratory Medicine, 5 Pediatrics, and 6 Surgery, Brown Medical School, Providence, Rhode Island 02905
Submitted 1 April 2004
; accepted in final form 19 May 2004
Postcanalicular lung development is characterized by a time-specific increase in alveolar epithelial type II cell apoptosis. We have previously demonstrated that, in fetal rabbits, developmental type II cell apoptosis coincides with transient upregulation of the cell death regulator Fas ligand (FasL). The aims of this study were 1 ) to determine the spatiotemporal patterns of pulmonary apoptosis and Fas / FasL gene expression in the murine model [embryonic day 17 (E17) through postnatal day 5 (P5)], and 2 ) to investigate the functional involvement of the Fas/FasL system by determining the effect of Fas activation and inhibition on perinatal pulmonary apoptosis. The apoptotic activity of alveolar epithelial type II cells, determined by combined TUNEL labeling and anti-surfactant protein B immunohistochemistry, showed a dramatic increase during the perinatal transition (type II cell apoptotic index |
| doi_str_mv | 10.1152/ajplung.00120.2004 |
| format | Article |
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Submitted 1 April 2004
; accepted in final form 19 May 2004
Postcanalicular lung development is characterized by a time-specific increase in alveolar epithelial type II cell apoptosis. We have previously demonstrated that, in fetal rabbits, developmental type II cell apoptosis coincides with transient upregulation of the cell death regulator Fas ligand (FasL). The aims of this study were 1 ) to determine the spatiotemporal patterns of pulmonary apoptosis and Fas / FasL gene expression in the murine model [embryonic day 17 (E17) through postnatal day 5 (P5)], and 2 ) to investigate the functional involvement of the Fas/FasL system by determining the effect of Fas activation and inhibition on perinatal pulmonary apoptosis. The apoptotic activity of alveolar epithelial type II cells, determined by combined TUNEL labeling and anti-surfactant protein B immunohistochemistry, showed a dramatic increase during the perinatal transition (type II cell apoptotic index <0.1% at E17, 1.5% at P1-P3, and 0.3% at P5). This timing of enhanced type II cell apoptosis coincided with a robust 14-fold increase in Fas mRNA and protein levels and a threefold increase in FasL protein levels; both Fas and FasL immunolocalized to type II and bronchial epithelial cells. In vitro and in vivo exposure of fetal and postnatal murine type II cells to anti-Fas antibody induced a fourfold increase in apoptotic activity that was prevented by administration of a broad-spectrum caspase inhibitor; the pulmonary apoptotic activity of Fas-deficient lpr mice remained unchanged. Conversely, administration of a caspase inhibitor to newborn mice (P1) resulted in marked diminution of pulmonary apoptotic activity. These combined findings strongly implicate the Fas/FasL system as a critical regulator of perinatal type II cell apoptosis. The developmental time dependence of apoptosis-related events in the murine model should facilitate investigations of the regulation of perinatal pulmonary apoptotic gene expression.
programmed cell death; lpr ; CD95; lung development
Address for reprint requests and other correspondence: M. E. De Paepe, Women and Infants Hospital, Dept. of Pathology, 101 Dudley St., Providence, RI 02905 (E-mail: mdepaepe{at}wihri.org )</description><identifier>ISSN: 1040-0605</identifier><identifier>EISSN: 1522-1504</identifier><identifier>DOI: 10.1152/ajplung.00120.2004</identifier><identifier>PMID: 15355863</identifier><language>eng</language><publisher>United States</publisher><subject>Aging ; Amino Acid Chloromethyl Ketones - pharmacology ; Animals ; Animals, Newborn ; Apoptosis - physiology ; Caspase Inhibitors ; Cysteine Proteinase Inhibitors - pharmacology ; Fas Ligand Protein ; fas Receptor - genetics ; fas Receptor - physiology ; In Situ Nick-End Labeling ; Lung - cytology ; Lung - embryology ; Lung - growth & development ; Lung - physiology ; Membrane Glycoproteins - deficiency ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout</subject><ispartof>American journal of physiology. Lung cellular and molecular physiology, 2004-10, Vol.287 (4), p.L730-L742</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-2fafce794492eef792596950ee038c340547aab92fd48c24d9b01b9f70273e853</citedby><cites>FETCH-LOGICAL-c387t-2fafce794492eef792596950ee038c340547aab92fd48c24d9b01b9f70273e853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3039,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15355863$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>De Paepe, Monique E</creatorcontrib><creatorcontrib>Mao, Quanfu</creatorcontrib><creatorcontrib>Embree-Ku, Michelle</creatorcontrib><creatorcontrib>Rubin, Lewis P</creatorcontrib><creatorcontrib>Luks, Francois I</creatorcontrib><title>Fas/FasL-mediated apoptosis in perinatal murine lungs</title><title>American journal of physiology. Lung cellular and molecular physiology</title><addtitle>Am J Physiol Lung Cell Mol Physiol</addtitle><description>1 Program in Fetal Medicine, Departments of 2 Pathology and 4 Pediatrics, Women and Infants Hospital, Providence 02905; and Departments of 3 Pathology and Laboratory Medicine, 5 Pediatrics, and 6 Surgery, Brown Medical School, Providence, Rhode Island 02905
Submitted 1 April 2004
; accepted in final form 19 May 2004
Postcanalicular lung development is characterized by a time-specific increase in alveolar epithelial type II cell apoptosis. We have previously demonstrated that, in fetal rabbits, developmental type II cell apoptosis coincides with transient upregulation of the cell death regulator Fas ligand (FasL). The aims of this study were 1 ) to determine the spatiotemporal patterns of pulmonary apoptosis and Fas / FasL gene expression in the murine model [embryonic day 17 (E17) through postnatal day 5 (P5)], and 2 ) to investigate the functional involvement of the Fas/FasL system by determining the effect of Fas activation and inhibition on perinatal pulmonary apoptosis. The apoptotic activity of alveolar epithelial type II cells, determined by combined TUNEL labeling and anti-surfactant protein B immunohistochemistry, showed a dramatic increase during the perinatal transition (type II cell apoptotic index <0.1% at E17, 1.5% at P1-P3, and 0.3% at P5). This timing of enhanced type II cell apoptosis coincided with a robust 14-fold increase in Fas mRNA and protein levels and a threefold increase in FasL protein levels; both Fas and FasL immunolocalized to type II and bronchial epithelial cells. In vitro and in vivo exposure of fetal and postnatal murine type II cells to anti-Fas antibody induced a fourfold increase in apoptotic activity that was prevented by administration of a broad-spectrum caspase inhibitor; the pulmonary apoptotic activity of Fas-deficient lpr mice remained unchanged. Conversely, administration of a caspase inhibitor to newborn mice (P1) resulted in marked diminution of pulmonary apoptotic activity. These combined findings strongly implicate the Fas/FasL system as a critical regulator of perinatal type II cell apoptosis. The developmental time dependence of apoptosis-related events in the murine model should facilitate investigations of the regulation of perinatal pulmonary apoptotic gene expression.
programmed cell death; lpr ; CD95; lung development
Address for reprint requests and other correspondence: M. E. De Paepe, Women and Infants Hospital, Dept. of Pathology, 101 Dudley St., Providence, RI 02905 (E-mail: mdepaepe{at}wihri.org )</description><subject>Aging</subject><subject>Amino Acid Chloromethyl Ketones - pharmacology</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Apoptosis - physiology</subject><subject>Caspase Inhibitors</subject><subject>Cysteine Proteinase Inhibitors - pharmacology</subject><subject>Fas Ligand Protein</subject><subject>fas Receptor - genetics</subject><subject>fas Receptor - physiology</subject><subject>In Situ Nick-End Labeling</subject><subject>Lung - cytology</subject><subject>Lung - embryology</subject><subject>Lung - growth & development</subject><subject>Lung - physiology</subject><subject>Membrane Glycoproteins - deficiency</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - physiology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><issn>1040-0605</issn><issn>1522-1504</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kD1PwzAURS0EoqXwBxhQJra0L_6I4xFVFJAqsZTZcpKX1lW-iBNB_z0uDerEYPlJvufaPoTcRzCPIkEXZt-WQ72dA0QU5hSAX5CpP6BhJIBf-hk4hBCDmJAb5_YAIADiazKJBBMiidmUiJVxC7_WYYW5NT3mgWmbtm-cdYGtgxY7W5velEE1-AmD443ullwVpnR4N-4z8rF63ixfw_X7y9vyaR1mLJF9SAtTZCgV54oiFlJRoWIlABFYkjEOgktjUkWLnCcZ5blKIUpVIYFKholgM_J46m275nNA1-vKugzL0tTYDE7HcSJikNQH6SmYdY1zHRa67WxluoOOQB9l6VGW_pWlj7I89DC2D6n__RkZ7fiAOgV2drv7sh3qdndwtimb7UGvhrLc4Hf_10wTqbleSwa6zQvPhv-zf485M-wHanyLQg</recordid><startdate>20041001</startdate><enddate>20041001</enddate><creator>De Paepe, Monique E</creator><creator>Mao, Quanfu</creator><creator>Embree-Ku, Michelle</creator><creator>Rubin, Lewis P</creator><creator>Luks, Francois I</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20041001</creationdate><title>Fas/FasL-mediated apoptosis in perinatal murine lungs</title><author>De Paepe, Monique E ; Mao, Quanfu ; Embree-Ku, Michelle ; Rubin, Lewis P ; Luks, Francois I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-2fafce794492eef792596950ee038c340547aab92fd48c24d9b01b9f70273e853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Aging</topic><topic>Amino Acid Chloromethyl Ketones - pharmacology</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Apoptosis - physiology</topic><topic>Caspase Inhibitors</topic><topic>Cysteine Proteinase Inhibitors - pharmacology</topic><topic>Fas Ligand Protein</topic><topic>fas Receptor - genetics</topic><topic>fas Receptor - physiology</topic><topic>In Situ Nick-End Labeling</topic><topic>Lung - cytology</topic><topic>Lung - embryology</topic><topic>Lung - growth & development</topic><topic>Lung - physiology</topic><topic>Membrane Glycoproteins - deficiency</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Membrane Glycoproteins - physiology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>De Paepe, Monique E</creatorcontrib><creatorcontrib>Mao, Quanfu</creatorcontrib><creatorcontrib>Embree-Ku, Michelle</creatorcontrib><creatorcontrib>Rubin, Lewis P</creatorcontrib><creatorcontrib>Luks, Francois I</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of physiology. Lung cellular and molecular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>De Paepe, Monique E</au><au>Mao, Quanfu</au><au>Embree-Ku, Michelle</au><au>Rubin, Lewis P</au><au>Luks, Francois I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fas/FasL-mediated apoptosis in perinatal murine lungs</atitle><jtitle>American journal of physiology. Lung cellular and molecular physiology</jtitle><addtitle>Am J Physiol Lung Cell Mol Physiol</addtitle><date>2004-10-01</date><risdate>2004</risdate><volume>287</volume><issue>4</issue><spage>L730</spage><epage>L742</epage><pages>L730-L742</pages><issn>1040-0605</issn><eissn>1522-1504</eissn><abstract>1 Program in Fetal Medicine, Departments of 2 Pathology and 4 Pediatrics, Women and Infants Hospital, Providence 02905; and Departments of 3 Pathology and Laboratory Medicine, 5 Pediatrics, and 6 Surgery, Brown Medical School, Providence, Rhode Island 02905
Submitted 1 April 2004
; accepted in final form 19 May 2004
Postcanalicular lung development is characterized by a time-specific increase in alveolar epithelial type II cell apoptosis. We have previously demonstrated that, in fetal rabbits, developmental type II cell apoptosis coincides with transient upregulation of the cell death regulator Fas ligand (FasL). The aims of this study were 1 ) to determine the spatiotemporal patterns of pulmonary apoptosis and Fas / FasL gene expression in the murine model [embryonic day 17 (E17) through postnatal day 5 (P5)], and 2 ) to investigate the functional involvement of the Fas/FasL system by determining the effect of Fas activation and inhibition on perinatal pulmonary apoptosis. The apoptotic activity of alveolar epithelial type II cells, determined by combined TUNEL labeling and anti-surfactant protein B immunohistochemistry, showed a dramatic increase during the perinatal transition (type II cell apoptotic index <0.1% at E17, 1.5% at P1-P3, and 0.3% at P5). This timing of enhanced type II cell apoptosis coincided with a robust 14-fold increase in Fas mRNA and protein levels and a threefold increase in FasL protein levels; both Fas and FasL immunolocalized to type II and bronchial epithelial cells. In vitro and in vivo exposure of fetal and postnatal murine type II cells to anti-Fas antibody induced a fourfold increase in apoptotic activity that was prevented by administration of a broad-spectrum caspase inhibitor; the pulmonary apoptotic activity of Fas-deficient lpr mice remained unchanged. Conversely, administration of a caspase inhibitor to newborn mice (P1) resulted in marked diminution of pulmonary apoptotic activity. These combined findings strongly implicate the Fas/FasL system as a critical regulator of perinatal type II cell apoptosis. The developmental time dependence of apoptosis-related events in the murine model should facilitate investigations of the regulation of perinatal pulmonary apoptotic gene expression.
programmed cell death; lpr ; CD95; lung development
Address for reprint requests and other correspondence: M. E. De Paepe, Women and Infants Hospital, Dept. of Pathology, 101 Dudley St., Providence, RI 02905 (E-mail: mdepaepe{at}wihri.org )</abstract><cop>United States</cop><pmid>15355863</pmid><doi>10.1152/ajplung.00120.2004</doi></addata></record> |
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| source | MEDLINE; American Physiological Society Paid; EZB-FREE-00999 freely available EZB journals |
| subjects | Aging Amino Acid Chloromethyl Ketones - pharmacology Animals Animals, Newborn Apoptosis - physiology Caspase Inhibitors Cysteine Proteinase Inhibitors - pharmacology Fas Ligand Protein fas Receptor - genetics fas Receptor - physiology In Situ Nick-End Labeling Lung - cytology Lung - embryology Lung - growth & development Lung - physiology Membrane Glycoproteins - deficiency Membrane Glycoproteins - genetics Membrane Glycoproteins - physiology Mice Mice, Inbred C57BL Mice, Knockout |
| title | Fas/FasL-mediated apoptosis in perinatal murine lungs |
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