{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:38:58Z","timestamp":1790919538576,"version":"4.1.0"},"reference-count":67,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2012,12,1]],"date-time":"2012-12-01T00:00:00Z","timestamp":1354320000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The lung is the site of entry for\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Bacillus anthracis<\/jats:named-content>\n                    in inhalation anthrax, the deadliest form of the disease.\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Bacillus anthracis<\/jats:named-content>\n                    produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Bacillus anthracis<\/jats:named-content>\n                    virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. Our current results suggest that, unlike human alveolar macrophages, the cells lining the respiratory units of the lung, alveolar epithelial cells, are a target of lethal toxin in humans. Alveolar epithelial cells expressed lethal toxin receptor protein, bound the protective antigen component of lethal toxin, and were subject to lethal-toxin-induced cleavage of multiple MEKs. These findings suggest that human alveolar epithelial cells are a target of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Bacillus anthracis<\/jats:named-content>\n                    lethal toxin. Further, no reduction in alveolar epithelial cell viability was observed, but lethal toxin caused actin rearrangement and impaired desmosome formation, consistent with impaired barrier function as well as reduced surfactant production. Therefore, by compromising epithelial barrier function, lethal toxin may play a role in the pathogenesis of inhalation anthrax by facilitating the dissemination of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Bacillus anthracis<\/jats:named-content>\n                    from the lung in early disease and promoting edema in late stages of the illness.\n                  <\/jats:p>","DOI":"10.1128\/iai.01011-12","type":"journal-article","created":{"date-parts":[[2012,10,2]],"date-time":"2012-10-02T02:04:49Z","timestamp":1349143489000},"page":"4374-4387","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Bacillus anthracis Lethal Toxin Reduces Human Alveolar Epithelial Barrier Function"],"prefix":"10.1128","volume":"80","author":[{"given":"Marybeth","family":"Langer","sequence":"first","affiliation":[{"name":"Pulmonary and Critical Care Division of the Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth Stewart","family":"Duggan","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division of the Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Leland","family":"Booth","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division of the Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineet Indrajit","family":"Patel","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division of the Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan A.","family":"Zander","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division of the Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Silasi-Mansat","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Ramani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tibor Zoltan","family":"Veres","sequence":"additional","affiliation":[{"name":"MediCity Research Laboratory, University of Turku, Turku, Finland, Hanover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Prenzler","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Toxicology and Experimental Medicine, Hanover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherina","family":"Sewald","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Toxicology and Experimental Medicine, Hanover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Williams","sequence":"additional","affiliation":[{"name":"Civil Aerospace Medical Institute, Federal Aviation Administration, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth Mark","family":"Coggeshall","sequence":"additional","affiliation":[{"name":"Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanjana","family":"Awasthi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florea","family":"Lupu","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Burian","sequence":"additional","affiliation":[{"name":"Civil Aerospace Medical Institute, Federal Aviation Administration, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy Dale","family":"Ballard","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Braun","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Toxicology and Experimental Medicine, Hanover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan Patrick","family":"Metcalf","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division of the Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA"},{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100249"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/arrd.1977.116.4.589"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.7.863"},{"key":"e_1_3_2_5_2","first-page":"R728","article-title":"Microsphere and dilution techniques for the determination of blood flows and volumes in conscious mice","volume":"263","author":"Barbee RW","year":"1992","unstructured":"BarbeeRWPerryBDReRNMurgoJP. 1992. Microsphere and dilution techniques for the determination of blood flows and volumes in conscious mice. Am. J. Physiol. 263:R728\u2013R733.","journal-title":"Am. J. Physiol."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1139\/o59-099"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00582.2004"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.20.2554"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00346-09"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21555"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2033"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00446-06"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700095"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.05.048"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2010.10.009"},{"key":"e_1_3_2_16_2","first-page":"740","article-title":"Cell number and cell characteristics of the normal human lung","volume":"125","author":"Crapo JD","year":"1982","unstructured":"CrapoJDBarryBEGehrPBachofenMWeibelER. 1982. Cell number and cell characteristics of the normal human lung. Am. Rev. Respir. Dis. 125:740\u2013745.","journal-title":"Am. Rev. Respir. Dis."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.107.2.443"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/002215549904700202"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.91.4.1487"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601687"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018887501927"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.45.3.761-767.1984"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00178.2005"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.1.245-252.1993"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-002-0653-5"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12450"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(02)02422-8"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705317"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2007.07.012"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10544-011-9570-2"},{"key":"e_1_3_2_31_2","first-page":"76","article-title":"The type II epithelial cell of the lung. I. Method of isolation","volume":"30","author":"Kikkawa Y","year":"1974","unstructured":"KikkawaYYonedaK. 1974. The type II epithelial cell of the lung. I. Method of isolation. Lab. Invest. 30:76\u201384.","journal-title":"Lab. Invest."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2007.12.001"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004755"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408122200"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905409106"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.10.004"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.19.9.2251"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.8.4801-4809.2004"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00023-06"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011110-130158"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17991"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2009.07.003"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(83)90116-X"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.9.3818-3826.1996"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.457"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073163"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.118.3.681"},{"key":"e_1_3_2_49_2","first-page":"2215","article-title":"Cellular F-actin levels as a marker for cellular transformation: relationship to cell division and differentiation","volume":"50","author":"Rao JY","year":"1990","unstructured":"RaoJY. 1990. Cellular F-actin levels as a marker for cellular transformation: relationship to cell division and differentiation. Cancer Res. 50:2215\u20132220.","journal-title":"Cancer Res."},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02714430"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016482"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00186-09"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01438.x"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1700730219"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.10.046"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(80)90269-9"},{"key":"e_1_3_2_57_2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/978-1-61779-191-8_13","volume-title":"Permeability barrier: methods and protocols","author":"Strengert M","year":"2011","unstructured":"StrengertMKnausUG. 2011. Analysis of epithelial barrier integrity in polarized lung epithelial cells, p 195\u2013206. In TurksenK (ed), Permeability barrier: methods and protocols, vol 763. Springer, New York, NY."},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1989.257.3.C528"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2009.184"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2012.07.022"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0410OC"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2003.09.002"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62496-0"},{"key":"e_1_3_2_64_2","first-page":"137","article-title":"Isolation and culture of human alveolar type II pneumocytes","volume":"56","author":"Witherden IR","year":"2001","unstructured":"WitherdenIRTetleyTD. 2001. Isolation and culture of human alveolar type II pneumocytes. Methods Mol. Med. 56:137\u2013146.","journal-title":"Methods Mol. Med."},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803406"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200111)44:11<2642::AID-ART444>3.0.CO;2-8"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900650"},{"key":"e_1_3_2_68_2","volume-title":"Biostatistical analysis.","author":"Zar JH","year":"1996","unstructured":"ZarJH. 1996. Biostatistical analysis. Prentice-Hall, Englewood Cliffs, NJ."}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01011-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01011-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T07:02:59Z","timestamp":1646463779000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.01011-12"}},"subtitle":[],"editor":[{"given":"S. R.","family":"Blanke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,12]]},"references-count":67,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["10.1128\/IAI.01011-12"],"URL":"https:\/\/doi.org\/10.1128\/iai.01011-12","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12]]},"assertion":[{"value":"2012-09-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-09-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-11-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}