{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:27:45Z","timestamp":1760549265286},"reference-count":60,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,10,29]],"date-time":"2012-10-29T00:00:00Z","timestamp":1351468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypoxemic respiratory failure of the neonatal organism involves increased acid sphingomyelinase (a<jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>ase) activity and production of ceramide, a second messenger of a pro\u2010inflammatory pathway that promotes increased vascular permeability, surfactant alterations and alveolar epithelial apoptosis. We comparatively assessed the benefits of topical a<jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>ase inhibition by either imipramine (Imi) or phosphatidylinositol\u20103,5\u2010bisphosphate (<jats:styled-content style=\"fixed-case\">PIP<\/jats:styled-content>2) when administered into the airways together with surfactant (S) for fortification. In this translational study, a triple\u2010hit acute lung injury model was used that entails repeated airway lavage, injurious ventilation and tracheal lipopolysaccharide instillation in newborn piglets subject to mechanical ventilation for 72\u00a0hrs. After randomization, we administered an air bolus (control), S, S+Imi, or S+<jats:styled-content style=\"fixed-case\">PIP<\/jats:styled-content>2. Only in the latter two groups we observed significantly improved oxygenation and ventilation, dynamic compliance and pulmonary oedema. S+Imi caused systemic a<jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>ase suppression and ceramide reduction, whereas the S+PIP2 effect remained compartmentalized in the airways because of the molecule's bulky structure. The surfactant surface tensions improved by S+Imi and S+PIP2 interventions, but only to a minor extent by S alone. S+<jats:styled-content style=\"fixed-case\">PIP<\/jats:styled-content>2 inhibited the migration of monocyte\u2010derived macrophages and granulocytes into airways by the reduction of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>14\/<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>18 expression on cell membranes and the expression of epidermal growth factors (amphiregulin and <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b21) and interleukin\u20106 as pro\u2010fibrotic factors. Finally we observed reduced alveolar epithelial apoptosis, which was most apparent in S+<jats:styled-content style=\"fixed-case\">PIP<\/jats:styled-content>2 lungs. Exogenous surfactant \u201cfortified\u201d by <jats:styled-content style=\"fixed-case\">PIP<\/jats:styled-content>2, a naturally occurring surfactant component, improves lung function by topical suppression of a<jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>ase, providing a potential treatment concept for neonates with hypoxemic respiratory failure.<\/jats:p>","DOI":"10.1111\/j.1582-4934.2012.01618.x","type":"journal-article","created":{"date-parts":[[2012,8,8]],"date-time":"2012-08-08T11:21:08Z","timestamp":1344424868000},"page":"2813-2826","source":"Crossref","is-referenced-by-count":9,"title":["Topical application of phosphatidyl\u2010inositol\u20103,5\u2010bisphosphate for acute lung injury in neonatal swine"],"prefix":"10.1111","volume":"16","author":[{"given":"Stefanie","family":"Preu\u00df","sequence":"first","affiliation":[{"name":"Universit\u00e4tsklinikum Schleswig\u2010Holstein, Campus Kiel Department of Pediatrics Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friede D.","family":"Omam","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Schleswig\u2010Holstein, Campus Kiel Department of Pediatrics Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Scheiermann","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Schleswig\u2010Holstein, Campus Kiel Department of Pediatrics Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Stadelmann","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Schleswig\u2010Holstein, Campus Kiel Department of Pediatrics Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Supandi","family":"Winoto\u2010Morbach","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Schleswig\u2010Holstein, Campus Kiel Institute of Immunology Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"von Bismarck","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Schleswig\u2010Holstein, Campus Kiel Department of Pediatrics Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Adam\u2010Klages","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Schleswig\u2010Holstein, Campus Kiel Institute of Immunology Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friederike","family":"Knerlich\u2010Lukoschus","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Schleswig\u2010Holstein, Campus Kiel Department of Neurosurgery Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"Lex","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum, RWTH Aachen Institute of Pharmacology and Toxicology Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Wesch","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Schleswig\u2010Holstein, Campus Kiel Institute of Immunology Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janka","family":"Held\u2010Feindt","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Schleswig\u2010Holstein, Campus Kiel Department of Neurosurgery Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Uhlig","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum, RWTH Aachen Institute of Pharmacology and Toxicology Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Sch\u00fctze","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Schleswig\u2010Holstein, Campus Kiel Institute of Immunology Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin F.","family":"Krause","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Schleswig\u2010Holstein, Campus Kiel Department of Pediatrics Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,10,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-7-100"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200705-752OC"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2001.281.1.L98"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00184.2002"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm977"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401382"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.22.4.3376"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSS0740129"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2005.11.013"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2003.144"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200903288"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200107000-00009"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2842fje"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/NMETH894"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90275-5"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5307"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00320.2007"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-3283"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.293.4.470"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201009-1424OC"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5497.1721"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0216127"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010666200"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.16.5.9160843"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00169"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2011.01.022"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.192.61"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3600513"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0078OC"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.5.4.723-731.2006"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/PCC.0b013e3181d5063c"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000103930.93849.B2"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200504-031AC"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00357-9"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.3.2003065"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2010.326"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc1861"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/01902140590918759"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.137604"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2009.01.014"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2001.280.1.L58"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.10.5439"},{"key":"e_1_2_8_44_1","doi-asserted-by":"crossref","first-page":"5704","DOI":"10.4049\/jimmunol.161.10.5704","article-title":"The role of leukocyte emigration and IL\u20108 on the development of lipopolysaccharide\u2010induced lung injury in rabbits","volume":"161","author":"Yamamoto T","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2011.11.004"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00110.2005"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200806-975OC"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401171"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2002-0092OC"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-004-2503-2"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.139.2.703"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181f3e076"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00292.2011"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-1536-4-12"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00275.2005"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706173"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.04.005"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0262OC"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00258.2002"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-8-51"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2007.040584"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1582-4934.2012.01618.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1582-4934.2012.01618.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T17:13:04Z","timestamp":1698685984000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1582-4934.2012.01618.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10,29]]},"references-count":60,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2012,11]]}},"alternative-id":["10.1111\/j.1582-4934.2012.01618.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1582-4934.2012.01618.x","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10,29]]}}}