{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:31:01Z","timestamp":1791297061497,"version":"4.1.0"},"reference-count":55,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,2,19]]},"abstract":"<jats:p>\n                    Vascular dysfunction has been reported in human cases of anthrax, in mammalian models of\n                    <jats:italic>Bacillus anthracis<\/jats:italic>\n                    , and in animals injected with anthrax toxin proteins. To examine anthrax lethal toxin effects on intact blood vessels, we developed a zebrafish model that permits\n                    <jats:italic>in vivo<\/jats:italic>\n                    imaging and evaluation of vasculature and cardiovascular function. Vascular defects monitored in hundreds of embryos enabled us to define four stages of phenotypic progression leading to circulatory dysfunction. We demonstrated increased endothelial permeability as an early consequence of toxin action by tracking the extravasation of fluorescent microspheres in toxin-injected embryos. Lethal toxin did not induce a significant amount of cell death in embryonic tissues or blood vessels, as shown by staining with acridine orange, and endothelial cells in lethal toxin-injected embryos continued to divide at the normal rate. Vascular permeability is strongly affected by the VEGF\/vascular permeability factor (VPF) signaling pathway, and we were able to attenuate anthrax lethal toxin effects with chemical inhibitors of VEGFR function. Our study demonstrates the importance of vascular permeability in anthrax lethal toxin action and the need for further investigation of the cardiovascular component of human anthrax disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0712195105","type":"journal-article","created":{"date-parts":[[2008,2,11]],"date-time":"2008-02-11T21:40:28Z","timestamp":1202766028000},"page":"2439-2444","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":51,"title":["Anthrax lethal toxin induces cell death-independent permeability in zebrafish vasculature"],"prefix":"10.1073","volume":"105","author":[{"suffix":"III","given":"Robert E.","family":"Bolcome","sequence":"first","affiliation":[{"name":"*Vascular Biology Program, Children's Hospital Boston and Department of Surgery, Harvard Medical School, Boston, MA 02115; and"},{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"*Vascular Biology Program, Children's Hospital Boston and Department of Surgery, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Zeller","sequence":"additional","affiliation":[{"name":"*Vascular Biology Program, Children's Hospital Boston and Department of Surgery, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam P.","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. John","family":"Collier","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Chan","sequence":"additional","affiliation":[{"name":"*Vascular Biology Program, Children's Hospital Boston and Department of Surgery, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,2,19]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63697-8"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0706.010604"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16769-X"},{"key":"e_1_3_3_4_2","first-page":"336","article-title":"On the histopathology of experimental anthrax in the guinea-pig.","volume":"36","author":"Ross JM","year":"1955","unstructured":"JM Ross, On the histopathology of experimental anthrax in the guinea-pig. Br J Exp Pathol 36, 336\u2013339 (1955).","journal-title":"Br J Exp Pathol"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/116.3.377"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.051330"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200317991"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/apm.1964.60.1.108"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.83.6.1274-1280.1962"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61218-7"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/510856"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.2.1266-1272.2006"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/n35101999"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0431098100"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401292200"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.1.430-439.2004"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62496-0"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9995"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2002.0711"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.12.3009"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1007"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2005.11.026"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2091"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1063654"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1002030302"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5364.734"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2003.08.012"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1086\/432731"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00490-07"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1113380"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.11.134"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.123.1.229"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mn.7800164"},{"key":"e_1_3_3_34_2","first-page":"2178","article-title":"PTK787\/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration.","volume":"60","author":"Wood JM","year":"2000","unstructured":"JM Wood, et al., PTK787\/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res 60, 2178\u20132189 (2000).","journal-title":"Cancer Res"},{"key":"e_1_3_3_35_2","first-page":"957","article-title":"Treatment for malignant pleural effusion of human lung adenocarcinoma by inhibition of vascular endothelial growth factor receptor tyrosine kinase phosphorylation.","volume":"6","author":"Yano S","year":"2000","unstructured":"S Yano, et al., Treatment for malignant pleural effusion of human lung adenocarcinoma by inhibition of vascular endothelial growth factor receptor tyrosine kinase phosphorylation. Clin Cancer Res 6, 957\u2013965 (2000).","journal-title":"Clin Cancer Res"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(02)00042-9"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio778"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1530\/rep.0.1250337"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2001-12-0350"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1068"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(04)76021-5"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(00)00051-2"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501368200"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi962553l"},{"key":"e_1_3_3_45_2","first-page":"2203","article-title":"Induction of apoptosis and inhibition of small cell lung cancer growth by the quinoxaline tyrphostins.","volume":"57","author":"Krystal GW","year":"1997","unstructured":"GW Krystal, P Carlson, J Litz, Induction of apoptosis and inhibition of small cell lung cancer growth by the quinoxaline tyrphostins. Cancer Res 57, 2203\u20132208 (1997).","journal-title":"Cancer Res"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/40187"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(03)00658-9"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00542.2005"},{"key":"e_1_3_3_49_2","first-page":"47","article-title":"A proposal linking clearance of circulating lipoproteins to tissue metabolic activity as a basis for understanding atherogenesis.","author":"Wolinsky H","year":"1980","unstructured":"H Wolinsky, A proposal linking clearance of circulating lipoproteins to tissue metabolic activity as a basis for understanding atherogenesis. Circ Res, pp. 47 (1980).","journal-title":"Circ Res"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1911"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1307"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210198"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80221-X"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/84675"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1195-1143"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0712195105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T16:23:16Z","timestamp":1649780596000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0712195105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2,19]]},"references-count":55,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2008,2,19]]}},"alternative-id":["10.1073\/pnas.0712195105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0712195105","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,2,19]]},"assertion":[{"value":"2007-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-02-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}