{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T20:36:01Z","timestamp":1774125361000,"version":"3.50.1"},"reference-count":53,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:p>We addressed the in vivo role of phosphatidylinositol 3-kinase-\u03b3 (PI3K-\u03b3) in signaling the sequestration of polymorphonuclear leukocytes (PMNs) in lungs and in the mechanism of inflammatory lung vascular injury. We studied mice with deletion of the p110 catalytic subunit of PI3K-\u03b3 (PI3K-\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup>mice). We measured lung tissue PMN sequestration, microvascular permeability, and edema formation after bacteremia induced by intraperitoneal Escherichia coli challenge. PMN infiltration into the lung interstitium in PI3K-\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup>mice as assessed morphometrically was increased 100% over that in control mice within 1 h after bacterial challenge. PI3K-\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup>mice also developed a greater increase in lung microvascular permeability after E. coli challenge, resulting in edema formation. The augmented lung tissue PMN sequestration in PI3K-\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup>mice was associated with increased expression of the PMN adhesive proteins CD47 and \u03b2<jats:sub>3<\/jats:sub>-integrins. We observed increased association of CD47 and \u03b2<jats:sub>3<\/jats:sub>-integrins with the extracellular matrix protein vitronectin in lungs of PI3K-\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup>mice after E. coli challenge. PMNs from these mice also showed increased \u03b2<jats:sub>3<\/jats:sub>-integrin expression and augmented \u03b2<jats:sub>3<\/jats:sub>-integrin-dependent PMN adhesion to vitronectin. These results point to a key role of PMN PI3K-\u03b3 in negatively regulating CD47 and \u03b2<jats:sub>3<\/jats:sub>-integrin expression in gram-negative sepsis. PI3K-\u03b3 activation in PMNs induced by E. coli may modulate the extent of lung tissue PMN sequestration secondary to CD47 and \u03b2<jats:sub>3<\/jats:sub>-integrin expression. Therefore, the level of PI3K-\u03b3 activation may be an important determinant of PMN-dependent lung vascular injury.<\/jats:p>","DOI":"10.1152\/ajplung.00179.2005","type":"journal-article","created":{"date-parts":[[2005,9,24]],"date-time":"2005-09-24T00:24:37Z","timestamp":1127521477000},"page":"L1094-L1103","source":"Crossref","is-referenced-by-count":27,"title":["Role of phosphatidylinositol 3-kinase-\u03b3 in mediating lung neutrophil sequestration and vascular injury induced by<i>E. coli<\/i>sepsis"],"prefix":"10.1152","volume":"289","author":[{"given":"Evan","family":"Ong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Pei","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Predescu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Broman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asrar B.","family":"Malik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.7.2137"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(89)90103-1"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200210115"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1172\/JCI13315"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.10.3251"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00023.2002"},{"key":"R7","unstructured":"Capodici C, Hanft S, Feoktistov M, and Pillinger MH.Phosphatidylinositol 3-kinase mediates chemoattractant-stimulated, CD11b\/CD18-dependent cell-cell adhesion of human neutrophils: evidence for an ERK-independent pathway.J Immunol160: 1901\u20131909, 1998."},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1038\/35004693"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.9.3978"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110054200"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.13.8554"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.135.2.533"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.1.21"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.5.2895"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.8.3974"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.146.3.673"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.108.5.1935"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.1.307"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052010699"},{"key":"R20","doi-asserted-by":"crossref","unstructured":"Harler MB, Wakshull E, Filardo EJ, Albina JE, and Reichner JS.Promotion of neutrophil chemotaxis through differential regulation of \u03b21and \u03b22integrins.J Immunol162: 6792\u20136799, 1999.","DOI":"10.4049\/jimmunol.162.11.6792"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.144.4.767"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5455.1049"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1987.67.4.1249"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1993.264.4.L401"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1006\/mvre.1995.1018"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1097\/00075198-200102000-00001"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0609.2000.90198.x"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.123.2.485"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5288.795"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.134.5.1313"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104138200"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109720200"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.132.3.437"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(00)01841-9"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1159\/000053589"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5455.1040"},{"key":"R37","doi-asserted-by":"crossref","unstructured":"Schwartz MA, Brown EJ, and Fazeli B.A 50-kDa integrin-associated protein is required for integrin-regulated calcium entry in endothelial cells.J Biol Chem268: 19931\u201319934, 1993.","DOI":"10.1016\/S0021-9258(20)80675-9"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5455.1037"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.50.3.616"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010898200"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-4310(00)01770-6"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90237-2"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80187-7"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(94)90093-0"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(99)00148-9"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.66.1.10"},{"key":"R47","unstructured":"Wagner JGand Roth RA.Neutrophil migration mechanisms, with an emphasis on the pulmonary vasculature.Pharmacol Rev52: 349\u2013374, 2000."},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1038\/ncb810"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.9.4.865"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005043421806"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.1.449"},{"key":"R52","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(00)01649-2"},{"key":"R53","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.3.254"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajplung.00179.2005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T19:20:39Z","timestamp":1683228039000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajplung.00179.2005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,12]]},"references-count":53,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2005,12]]}},"alternative-id":["10.1152\/ajplung.00179.2005"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00179.2005","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,12]]}}}