{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:34:03Z","timestamp":1773657243764,"version":"3.50.1"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[1998,1,1]],"date-time":"1998-01-01T00:00:00Z","timestamp":883612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We examined the ability of the human surfactant protein B (SP-B) promoter to confer cell specificity of transgene expression in an adenoviral vector. Using similar replication-deficient adenoviruses (rAd), we compared lacZ reporter gene expression driven by the human SP-B promoter (rAd.SPBlacZ) with the ubiquitously expressed Rous sarcoma virus promoter (rAd.RSVlacZ). rAd.SPBlacZ expressed lacZ in H-441 and A549 lung epithelial cell lines and not in HeLa cells whereas rAd.RSVlacZ expressed in all three cell lines. In primary human fetal lung fibroblasts, \u03b2-galactosidase activity from rAd.RSVlacZ transduction increased in a dose-dependent manner whereas activity from rAd.SPBlacZ remained low. In mixed cell cultures prepared from human fetal lung explants that contained fibroblasts and type II cells, X-Gal staining localized rAd.SPBlacZ expression to only type II cells whereas rAd.RSVlacZ expressed in both cell types. In 24-wk gestation human fetal tissue explants infected ex vivo, the RSV promoter directed lacZ expression in lung, trachea, heart, liver, and esophagus, whereas with the SP-B promoter lacZ was expressed only in lung, specifically in air space-lining cells. This specificity was maintained in vivo. lacZ expression was undetectable in lung and other tissues after intravenous administration of rAd.SPBlacZ whereas rAd.RSVlacZ expressed primarily in liver. After intratracheal instillation of rAd.SPBlacZ into mice, X-Gal staining localized expression to type II and Clara cells. In contrast, rAd.RSVlacZ expressed in all pulmonary epithelial cell types. Our results indicate that the SP-B promoter may be useful in targeting type II and Clara cells for gene therapy of conditions such as inherited deficiency of SP-B.<\/jats:p>","DOI":"10.1165\/ajrcmb.18.1.2878","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T22:09:58Z","timestamp":1365026998000},"page":"1-11","source":"Crossref","is-referenced-by-count":28,"title":["Targeting Type II and Clara Cells for Adenovirus-mediated Gene Transfer Using the Surfactant Protein B Promoter"],"prefix":"10.1093","volume":"18","author":[{"given":"Marlene S.","family":"Strayer","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Pennsylvania, and Children's Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan H.","family":"Guttentag","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pennsylvania, and Children's Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip L.","family":"Ballard","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pennsylvania, and Children's Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1998,1,1]]},"reference":[{"key":"2026030700175489700_B1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ng0593-27","article-title":"Direct gene transfer of human CF\u2009TR into human bronchial epithelia of xenografts with E1-deleted adenoviruses.","volume":"4","author":"Englehardt","year":"1993","journal-title":"Nature Genet."},{"key":"2026030700175489700_B2","doi-asserted-by":"crossref","first-page":"13695","DOI":"10.1016\/S0021-9258(17)36886-2","article-title":"In vivo correction of low density lipoprotein receptor deficiency in the Watanabe heritable hyperlipidemic rabbit with recombinant adenoviruses.","volume":"269","author":"Kozarsky","year":"1994","journal-title":"J. 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Res."},{"key":"2026030700175489700_B7","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/0378-1119(94)90025-6","article-title":"Expression vectors encoding human growth hormone (hGH) controlled by human muscle-specific promoters: prospects for regulated production of hGH delivered by myoblast transfer or intravenous injection.","volume":"145","author":"Dahler","year":"1994","journal-title":"Gene"},{"key":"2026030700175489700_B8","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1165\/ajrcmb\/9.3.231","article-title":"Cloning and tissue-specific expression of the cDNA for the mouse Clara cell 10 kD protein: comparison of endogenous expression to rabbit uteroglobin promoter-driven transgene expression.","volume":"9","author":"Margraf","year":"1993","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026030700175489700_B9","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1523\/JNEUROSCI.14-05-02455.1994","article-title":"Cell-specific expression from the human dopamine beta-hydroxylase promoter in transgenic mice is controlled via a combination of positive and negative regulatory elements.","volume":"14","author":"Hoyle","year":"1994","journal-title":"J. Neurosci."},{"key":"2026030700175489700_B10","first-page":"G1025","article-title":"A rat gastrin\u2013human gastrin chimeric transgene directs antral G cell-specific expression in transgenic mice.","volume":"268","author":"Wang","year":"1995","journal-title":"Am. J. 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Chem."},{"key":"2026030700175489700_B16","doi-asserted-by":"crossref","first-page":"19697","DOI":"10.1016\/S0021-9258(19)36572-X","article-title":"Identification of enhancers in the 5\u2032-flanking region of the rabbit surfactant protein A (SP-A) gene and characterization of their binding proteins.","volume":"268","author":"Gao","year":"1993","journal-title":"J. Biol. Chem."},{"key":"2026030700175489700_B17","doi-asserted-by":"crossref","first-page":"L674","DOI":"10.1152\/ajplung.1995.268.4.L674","article-title":"Characterization of the promoter of human pulmonary surfactant protein B gene. Am. J. Physiol. 268 (","volume":"12","author":"Venkatesh","year":"1995","journal-title":"Lung Cell. Mol. Physiol.)"},{"key":"2026030700175489700_B18","doi-asserted-by":"crossref","first-page":"6881","DOI":"10.1074\/jbc.271.12.6881","article-title":"Transcription of the lung-specific surfactant protein C gene is mediated by thyroid transcription factor 1.","volume":"271","author":"Kelly","year":"1996","journal-title":"J. Biol. Chem."},{"key":"2026030700175489700_B19","first-page":"1072","article-title":"Genomic elements involved in transcriptional regulation of the rabbit surfactant protein-A gene.","volume":"7","author":"Alcorn","year":"1993","journal-title":"Mol. Endocrinol."},{"key":"2026030700175489700_B20","doi-asserted-by":"crossref","first-page":"6122","DOI":"10.1073\/pnas.87.16.6122","article-title":"Cis-acting sequences from a human surfactant protein gene confer pulmonary-specific gene expression in transgenic mice.","volume":"87","author":"Korfhagen","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026030700175489700_B21","doi-asserted-by":"crossref","first-page":"12461","DOI":"10.1073\/pnas.92.26.12461","article-title":"Pulmonary malformation in transgenic mice expressing human keratinocyte growth factor in the lung.","volume":"92","author":"Simonet","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026030700175489700_B22","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1006\/dbio.1996.0110","article-title":"Arrested lung morphogenesis in transgenic mice bearing an SP-C-TGF-beta 1 chimeric gene.","volume":"175","author":"Zhou","year":"1996","journal-title":"Dev. Biol."},{"key":"2026030700175489700_B23","first-page":"5671","article-title":"The lung-specific surfactant protein B gene promoter is a target for thyroid transcription factor 1 and hepatocyte nuclear factor 3, indicating common factors for organ-specific gene expression along the foregut axis.","volume":"14","author":"Bohinski","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"2026030700175489700_B24","doi-asserted-by":"crossref","first-page":"24852","DOI":"10.1074\/jbc.270.42.24852","article-title":"Upstream enhancer activity in the human surfactant protein-B gene is mediated by thyroid transcription factor 1.","volume":"270","author":"Yan","year":"1995","journal-title":"J. Biol. Chem."},{"key":"2026030700175489700_B25","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1056\/NEJM199302113280606","article-title":"Brief report: Deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis.","volume":"328","author":"Nogee","year":"1993","journal-title":"New Engl. J. Med."},{"key":"2026030700175489700_B26","doi-asserted-by":"crossref","first-page":"334A","DOI":"10.1203\/00006450-199604001-02010","article-title":"Surfactant protein-B (SP-B) promoter in replication deficient adenovirus (rAd) directs pulmonary epithelial cell-specific gene expression.","volume":"39","author":"Guttentag","year":"1996","journal-title":"Pediatr. Res."},{"key":"2026030700175489700_B27","first-page":"5481","article-title":"Peripheral airway cell differentiation in human lung cancer cell lines.","volume":"50","author":"Gazdar","year":"1990","journal-title":"Cancer Res."},{"key":"2026030700175489700_B28","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1210\/jcem-62-4-678","article-title":"Glucocorticoids and thyroid hormones stimulate biochemical and morphological differentiation of human fetal lung in organ culture.","volume":"62","author":"Gonzales","year":"1986","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2026030700175489700_B29","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0304-4165(86)90326-0","article-title":"Isolation and characterization of differentiated alveolar type II cells from fetal human lung.","volume":"883","author":"Ballard","year":"1986","journal-title":"Biochim. Biophys. Acta"},{"key":"2026030700175489700_B30","first-page":"6169","article-title":"Ablation of E2A in recombinant adenoviruses improves transgene persistence and decreases inflammatory response in mouse liver.","volume":"91","author":"Englehardt","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026030700175489700_B31","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1258\/002367789780810536","article-title":"A method for intratracheal instillation of endotoxin into the lungs of mice.","volume":"23","author":"Starcher","year":"1989","journal-title":"Lab. Anim."},{"key":"2026030700175489700_B32","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1089\/hum.1997.8.8-919","article-title":"Enhanced distribution of adenovirus-mediated gene transfer to lung parenchyma by perfluorochemical liquid.","volume":"8","author":"Lisby","year":"1997","journal-title":"Hum. Gene Ther."},{"key":"2026030700175489700_B33","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1165\/ajrcmb\/7.4.368","article-title":"An antibody with specificity for surfactant protein C precursors: identification of ProSP-C in rat lung.","volume":"7","author":"Beers","year":"1992","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026030700175489700_B34","first-page":"993","article-title":"Two different factors act separately or together to specify functionally distinct activities on a single transcription enhancer.","volume":"6","author":"DeFranco","year":"1986","journal-title":"Mol. Cell. Biol."},{"key":"2026030700175489700_B35","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.","volume":"72","author":"Bradford","year":"1976","journal-title":"Ann. Biochem."},{"key":"2026030700175489700_B36","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/0167-4889(89)90201-2","article-title":"In vitro translation, posttranslational processing and secretion of pulmonary surfactant protein B precursors.","volume":"1011","author":"O'Reilly","year":"1989","journal-title":"Biochim. Biophys. 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USA"},{"key":"2026030700175489700_B40","doi-asserted-by":"crossref","first-page":"L178","DOI":"10.1152\/ajplung.1996.271.1.L178","article-title":"Distribution of alveolar type II cells in neonatal and adult rat lung revealed by RT-PCR in situ. Am. J. Physiol. 271 (","volume":"15","author":"Mensah","year":"1996","journal-title":"Lung Cell. Mol. Physiol.)"},{"key":"2026030700175489700_B41","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/BF00234174","article-title":"The distribution and structure of cells in the tracheal epithelium of the mouse.","volume":"208","author":"Pack","year":"1980","journal-title":"Cell Tissue Res."},{"key":"2026030700175489700_B42","first-page":"71","article-title":"The cells of the tracheobronchial epithelium of the mouse: a quantitative light and electron microscope study.","volume":"132","author":"Pack","year":"1981","journal-title":"J. Anat."},{"key":"2026030700175489700_B43","first-page":"553","article-title":"Relationship of cytochrome P-450 activity to Clara cell cytotoxicity. III. Morphometric comparison of changes in the epithelial populations of terminal bronchioles and lobar bronchi in mice, hamsters, and rats after parenteral administration of naphthalene.","volume":"67","author":"Plopper","year":"1992","journal-title":"Lab. Invest."},{"key":"2026030700175489700_B44","doi-asserted-by":"crossref","first-page":"985","DOI":"10.3109\/01902149109064330","article-title":"Localization of pulmonary surfactant proteins using immunohistochemistry and tissue in situ hybridization.","volume":"17","author":"Phelps","year":"1991","journal-title":"Exp. Lung Res."},{"key":"2026030700175489700_B45","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1177\/40.10.1527371","article-title":"The ontogeny and distribution of surfactant protein B in human fetuses and newborns.","volume":"40","author":"Stahlman","year":"1992","journal-title":"J. Histochem. Cytochem."},{"key":"2026030700175489700_B46","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1165\/ajrcmb.10.6.8003339","article-title":"Cell number and distribution in human and rat airways.","volume":"10","author":"Mercer","year":"1994","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026030700175489700_B47","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1056\/NEJM199605023341809","article-title":"Adenoviruses as gene-delivery vehicles.","volume":"334","author":"Wilson","year":"1996","journal-title":"New Engl. J. Med."},{"key":"2026030700175489700_B48","first-page":"S28","article-title":"Neonatal respiratory disease due to surfactant protein-B deficiency.","volume":"16","author":"Ballard","year":"1996","journal-title":"J. Perinatol."},{"key":"2026030700175489700_B49","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1542\/peds.96.6.1046","article-title":"Partial deficiency of surfactant protein-B in an infant with chronic lung disease.","volume":"96","author":"Ballard","year":"1995","journal-title":"Pediatrics"},{"key":"2026030700175489700_B50","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1165\/ajrcmb.16.1.8998078","article-title":"Pulmonary function in heterozygous and homozygous SP-B deficient mice.","volume":"16","author":"Clark","year":"1997","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026030700175489700_B51","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1165\/ajrcmb.11.2.8049084","article-title":"Ultrastructure of the lung in surfactant protein B deficiency.","volume":"11","author":"deMello","year":"1994","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026030700175489700_B52","doi-asserted-by":"crossref","first-page":"L647","DOI":"10.1152\/ajplung.1995.268.4.L647","article-title":"Aberrant processing of surfactant protein C in hereditary SP-B deficiency. Am. J. Physiol. 268(","volume":"12","author":"Vorbroker","year":"1995","journal-title":"Lung Cell. Mol. Physiol.)"},{"key":"2026030700175489700_B53","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/S0022-3476(05)83276-7","article-title":"Surfactant protein B deficiency: antenatal diagnosis and prospective treatment with surfactant replacement.","volume":"125","author":"Hamvas","year":"1994","journal-title":"J. Pediatr."},{"key":"2026030700175489700_B54","first-page":"29","article-title":"Immunocytochemical localization of the sites of superoxide dismutase induction by hyperoxia in rat lungs.","volume":"73","author":"Chang","year":"1995","journal-title":"Lab. Invest."},{"key":"2026030700175489700_B55","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1038\/nm0996-985","article-title":"Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer.","volume":"2","author":"Roth","year":"1996","journal-title":"Nature Med."},{"key":"2026030700175489700_B56","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1165\/ajrcmb.13.1.7598939","article-title":"Gene therapy using adenovirus carrying the herpes simplex-thymidine kinase gene to treat in vivo models of human malignant mesothelioma and lung cancer.","volume":"13","author":"Hwang","year":"1995","journal-title":"Am. J. Respir. Cell Mol. 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