{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T16:54:03Z","timestamp":1778000043509,"version":"3.51.4"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2004,2,1]],"date-time":"2004-02-01T00:00:00Z","timestamp":1075593600000},"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":[[2004,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Host defense mechanisms are impaired in patients with congenital neutrophil (polymorphonuclear neutrophils (PMN)) defects. Impaired PMN chemotaxis is observed in localized aggressive periodontitis (LAP), a familial disorder characterized by destruction of the supporting structures of dentition. In the present studies, we sought evidence for molecular events underlying this aberrant human PMN phenotype. To this end, PMN transendothelial migration and superoxide anion generation were assessed with LAP patients and asymptomatic family members, as well as patients with other chronic mucosal inflammation. PMN from LAP patients showed decreased transmigration across vascular endothelial monolayers (18 \u00b1 12% of control, n = 4) and increased superoxide anion generation (358 \u00b1 37%, p = 0.003). Gene expression was analyzed using oligonucleotide microarrays and fluorescence-based kinetic PCR. cDNA microarray and kinetic-PCR analysis revealed diminished RNA expression of leukocyte-type diacylglycerol (DAG) kinase \u03b1 in PMN from LAP patients (4.6 \u00b1 1.7 relative units, n = 6, p = 0.007) compared with asymptomatic individuals (51 \u00b1 27 relative units, n = 7). DAG kinase activity was monitored by DAG phosphorylation and individual DAG molecular species were quantified using liquid chromatography and tandem mass spectrometry-based lipidomics. DAG kinase activity was also significantly decreased (73 \u00b1 2%, p = 0.007) and correlated with increased accumulation of 1,2-diacyl-sn-3-glycerol substrates (p = 0.01). These results implicate defects in both PMN transendothelial migration and PMN DAG kinase \u03b1 signaling as disordered functions in LAP. Moreover, they identify a potential molecular lesion in PMN signal transduction that may account for their aberrant responses and tissue destruction in this disease.<\/jats:p>","DOI":"10.4049\/jimmunol.172.3.1856","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:08:36Z","timestamp":1398028116000},"page":"1856-1861","source":"Crossref","is-referenced-by-count":86,"title":["A Molecular Defect in Intracellular Lipid Signaling in Human Neutrophils in Localized Aggressive Periodontal Tissue Damage"],"prefix":"10.1093","volume":"172","author":[{"given":"Karsten","family":"Gronert","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alpdogan","family":"Kantarci","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine , Boston, MA 02118"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce D","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clary B","family":"Clish","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Odparlik","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hatice","family":"Hasturk","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine , Boston, MA 02118"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A","family":"Badwey","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean P","family":"Colgan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas E","family":"Van Dyke","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine , Boston, MA 02118"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles N","family":"Serhan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,2,1]]},"reference":[{"key":"2026020211201733500_R1","first-page":"27","volume-title":"N. 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