{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T15:28:46Z","timestamp":1760887726227,"version":"3.37.3"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2005,6,3]],"date-time":"2005-06-03T00:00:00Z","timestamp":1117756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK31056","HL76463","DE13499","DE16191","RR00533"],"award-info":[{"award-number":["DK31056","HL76463","DE13499","DE16191","RR00533"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In view of the reports that polymorphonuclear leukocytes (PMN) of patients with localized aggressive periodontitis (LAP) exhibit hyper-responsiveness to stimulation, it has been suggested that such abnormalities could lead to PMN-mediated tissue damage during inflammation. To determine whether these abnormalities include signal transduction, we compared cytoplasmic calcium concentration (\u0394[Ca2+]i) and cytoplasmic pH (\u0394pHi) changes, early stimulus responses to chemotactic agents, of LAP versus control (C)-PMN and explored whether these could be modulated by sensitizing cytokines or calcium channel-blocking agents. PMN responses of LAP patients were compared with age- and gender-matched controls. \u0394[Ca2+]i and \u0394pHi were measured fluorimetrically using 1H-indole-6-carboxylic acid, 2-[4-[bis[2-[(acetyloxy)methoxy]-2-oxoethyl]amino]-3-[2-[2-[bis[2-[(acetyloxy)methoxy]-2-oxoethyl]amino]-5-methylphenoxy]ethoxy]phenyl]-1 and 2\u2032,7\u2032-bis-(carboxyethyl)-5(6)-carboxyfluorescein as respective probes. Not only was the maximal calcium response to chemoattractants higher in LAP-PMN, but also their subsequent intracellular calcium redistribution was significantly slower. The slower calcium redistribution of LAP-PMN, but not their higher maximal calcium response, was successfully mimicked in C-PMN treated with Nifedipine\u2122 or 1-[b-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole-HCl, both known to be inhibitors of membrane-associated calcium influx, but this redistribution was not affected when inhibitors of other calcium influx mechanisms, Diltiazem\u2122 or Verapamil\u2122, were used. Taken together, our findings indicate that certain early stimulus responses are aberrant in LAP-PMN, that internal redistribution of cytoplasmic-free calcium is compromised, and, additionally, that a membrane-associated Ca2+ transport defect may be present.<\/jats:p>","DOI":"10.1189\/jlb.0105023","type":"journal-article","created":{"date-parts":[[2005,6,4]],"date-time":"2005-06-04T00:25:23Z","timestamp":1117844723000},"page":"612-619","source":"Crossref","is-referenced-by-count":10,"title":["Simultaneous measurements of cytoplasmic Ca2+ responses and intracellular pH in neutrophils of localized aggressive periodontitis (LAP) patients"],"prefix":"10.1093","volume":"78","author":[{"given":"Jens Martin","family":"Herrmann","sequence":"first","affiliation":[{"name":"Goldman School of Dental Medicinee, Boston University , Massachusetts"},{"name":"School of Medicine, Boston University , Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alpdogan","family":"Kantarci","sequence":"additional","affiliation":[{"name":"Goldman School of Dental Medicinee, Boston University , Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi","family":"Long","sequence":"additional","affiliation":[{"name":"School of Medicine, Boston University , Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Bernardo","sequence":"additional","affiliation":[{"name":"School of Medicine, Boston University , Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hatice","family":"Hasturk","sequence":"additional","affiliation":[{"name":"Goldman School of Dental Medicinee, Boston University , Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Lewis V","family":"Wray","sequence":"additional","affiliation":[{"name":"School of Medicine, Boston University , Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth R","family":"Simons","sequence":"additional","affiliation":[{"name":"School of Medicine, Boston University , Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas E","family":"Van Dyke","sequence":"additional","affiliation":[{"name":"Goldman School of Dental Medicinee, Boston University , Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2005,6,3]]},"reference":[{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1902\/jop.2003.74.1.66","article-title":"Neutrophil-mediated tissue injury in periodontal disease pathogenesis: findings from localized aggressive periodontitis","volume":"74","author":"Kantarci","year":"2003","journal-title":"J. Periodontol."},{"key":"2023033022371098400_","first-page":"465","article-title":"The oral\/dental\/craniofacial complex as a model for inflammatory disease","volume":"23","author":"Van Dyke","year":"2002","journal-title":"Compend. Contin. Educ. Dent."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1034\/j.1600-0757.2001.2260104.x","article-title":"Etiopathogenesis of periodontitis in children and adolescents","volume":"26","author":"Kinane","year":"2001","journal-title":"Periodontol. 2000"},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1034\/j.1600-0757.2001.2260105.x","article-title":"Influences of systemic diseases on periodontitis in children and adolescents","volume":"26","author":"Meyle","year":"2001","journal-title":"Periondontol. 2000"},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1034\/j.1600-051x.2001.028002162.x","article-title":"Altered chemotactic behavior of crevicular PMNs in different forms of periodontitis","volume":"28","author":"Sigusch","year":"2001","journal-title":"J. Clin. Periodontol."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1189\/jlb.72.6.1172","article-title":"Immune complex stimulation of human neutrophils involves a novel Ca2+\/H+ exchanger that participates in the regulation of cytoplasmic pH: flow cytometric analysis of Ca2+\/pH responses by subpopulations","volume":"72","author":"Bernardo","year":"2002","journal-title":"J. Leukoc. Biol."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/jlb.64.1.98","article-title":"Neutrophil degranulation and phospholipase D activation are enhanced if the Na+\/H+ antiport is blocked","volume":"64","author":"Gewirtz","year":"1998","journal-title":"J. Leukoc. Biol."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"9710","DOI":"10.1016\/S0021-9258(18)67572-6","article-title":"Simultaneous measurement of stimulus-induced changes in cytoplasmic Ca2+ and in membrane potential of human neutrophils","volume":"261","author":"Lazzari","year":"1986","journal-title":"J. Biol. Chem."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1002\/jlb.62.3.329","article-title":"A cytosolic calcium transient is not necessary for degranulation or oxidative burst in immune complex-stimulated neutrophils","volume":"62","author":"Seetoo","year":"1997","journal-title":"J. Leukoc. Biol."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"13035","DOI":"10.1016\/S0021-9258(18)98799-5","article-title":"Calcium changes in immune complex-stimulated human neutrophils. Simultaneous measurement of receptor occupancy and activation reveals full population stimulus binding but subpopulation activation","volume":"266","author":"Brunkhorst","year":"1991","journal-title":"J. Biol. Chem."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1046\/j.1365-2362.1996.126286.x","article-title":"Inhibited neutrophil functions in patients treated with nifedipine but not with Verapamil or Diltiazem","volume":"26","author":"Levy","year":"1996","journal-title":"Eur. J. Clin. Invest."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1042\/bj2710515","article-title":"SK&F 96365, a novel inhibitor of receptor-mediated calcium entry","volume":"271","author":"Merritt","year":"1990","journal-title":"Biochem. J."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1128\/iai.60.6.2481-2487.1992","article-title":"Altered diacylglycerol level and metabolism in neutrophils from patients with localized juvenile periodontitis","volume":"60","author":"Tyagi","year":"1992","journal-title":"Infect. Immun."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1128\/iai.61.8.3137-3142.1993","article-title":"Calcium-dependent protein kinase C activity of neutrophils in localized juvenile periodontitis","volume":"61","author":"Kurihara","year":"1993","journal-title":"Infect. Immun."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.4049\/jimmunol.172.3.1856","article-title":"A molecular defect in intracellular lipid signaling in human neutrophils in localized aggressive periodontal tissue damage","volume":"172","author":"Gronert","year":"2004","journal-title":"J. Immunol."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/j.1600-0765.1997.tb00550.x","article-title":"Evidence of an association between functional abnormalities and defective diacylglycerol kinase activity in peripheral blood neutrophils from patients with localized juvenile periodontitis","volume":"32","author":"Hurttia","year":"1997","journal-title":"J. Periodontal Res."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1111\/j.1600-0765.1994.tb01231.x","article-title":"Diacylglycerol in peripheral blood neutrophils from patients with localized juvenile periodontitis","volume":"29","author":"Leino","year":"1994","journal-title":"J. Periodontal Res."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.cellsig.2004.06.008","article-title":"CD38 cleavage in fMLP- and IL-8-induced chemotaxis is dependent on p38 MAP kinase but independent of p44\/42 MAP kinase","volume":"17","author":"Fujita","year":"2005","journal-title":"Cell. Signal."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1902\/jop.1993.64.7.617","article-title":"Defective chemotaxis and calcium response in localized juvenile periodontitis neutrophils","volume":"64","author":"Daniel","year":"1993","journal-title":"J. Periodontol."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1902\/jop.2000.71.5.797","article-title":"Defective calcium influx factor activity in neutrophils from patients with localized juvenile periodontitis","volume":"71","author":"Shibata","year":"2000","journal-title":"J. Periodontol."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/jcp.1041340206","article-title":"The role of transmembrane cationic gradients in immune complex stimulation of human polymorphonuclear leukocytes","volume":"134","author":"Luscinskas","year":"1988","journal-title":"J. Cell. Physiol."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1902\/annals.1999.4.1.1","article-title":"Development of a classification system for periodontal diseases and conditions","volume":"4","author":"Armitage","year":"1999","journal-title":"Ann. Periodontol."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1016\/S0021-9258(19)83641-4","article-title":"A new generation of Ca2+ indicators with greatly improved fluorescence properties","volume":"260","author":"Grynkiewicz","year":"1985","journal-title":"J. Biol. Chem."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/jlb.61.4.522","article-title":"Phospholipase D mediates Fc \u03b3 receptor activation of neutrophils and provides specificity between high-valency immune complexes and fMLP signaling pathways","volume":"61","author":"Gewirtz","year":"1997","journal-title":"J. Leukoc. Biol."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"17303","DOI":"10.1074\/jbc.272.28.17303","article-title":"Induction of tyrosine phosphorylation and Na+\/H+ exchanger activation during shrinkage of human neutrophils","volume":"272","author":"Krump","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0092-8674(89)90901-X","article-title":"Molecular cloning, primary structure, and expression of the human growth factor-activatable Na+\/H+ antiporter","volume":"56","author":"Sardet","year":"1989","journal-title":"Cell"},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1042\/cs0940461","article-title":"Neutrophil priming: pathophysiological consequences and underlying mechanisms","volume":"94","author":"Condliffe","year":"1998","journal-title":"Clin. Sci. (Lond.)"},{"key":"2023033022371098400_","doi-asserted-by":"crossref","first-page":"3601","DOI":"10.1016\/0006-2952(89)90133-0","article-title":"In vitro modulation of human neutrophil superoxide anion generation by various calcium channel antagonists used in ischemia-reperfusion resuscitation","volume":"38","author":"Zimmerman","year":"1989","journal-title":"Biochem. 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