{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:18:41Z","timestamp":1790738321159,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2006,12,1]],"date-time":"2006-12-01T00:00:00Z","timestamp":1164931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Tetracyclines are used in periodontal therapy as antimicrobial agents and as inhibitors of matrix metalloproteinases. Neutrophils appear to accumulate minocycline and other tetracyclines through a mechanism that has not been fully characterized.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The transport of minocycline and other tetracyclines by isolated human neutrophils was characterized by measuring the increase in cell\u2010associated fluorescence.<\/jats:p><jats:p><jats:bold>Results<\/jats:bold>: Quiescent neutrophils took up minocycline through a saturable, concentrative, sodium\u2010dependent mechanism with a Michaelis constant (K<jats:sub>m<\/jats:sub>) of 153 \u03bcg\/ml (501 \u03bcM) and a maximal velocity of 240 ng\/minute\/10<jats:sup>6<\/jats:sup> cells. The efficiency of minocycline transport was not influenced significantly by a two\u2010unit variation in extracellular pH and was not enhanced upon cell activation with phorbol myristate acetate. Neutrophil incubation in medium containing 10 \u03bcg\/ml minocycline, doxycycline, or tetracycline yielded steady\u2010state intracellular\/extracellular concentration ratios of \u223c64.0, 7.5, or 1.8, respectively. The dilution of extracellular minocycline or doxycycline triggered efflux from cells loaded with these antibiotics. Minocycline transport was competitively inhibited by the organic cations carnitine, diphenhydramine, and verapamil, but penicillin and other organic anions failed to produce inhibition.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Transport of tetracyclines by neutrophils could potentially enhance the effectiveness of these agents in periodontal therapy by enhancing or sustaining their therapeutic levels at inflammatory sites and by enhancing the killing of phagocytosed bacterial pathogens.<\/jats:p>","DOI":"10.1902\/jop.2006.060096","type":"journal-article","created":{"date-parts":[[2006,11,30]],"date-time":"2006-11-30T08:25:32Z","timestamp":1164875132000},"page":"1964-1968","source":"Crossref","is-referenced-by-count":14,"title":["Characterization of Minocycline Transport by Human Neutrophils"],"prefix":"10.1002","volume":"77","author":[{"given":"John D.","family":"Walters","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00271a020"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1981.52.10.613"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1985.56.11s.67"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1985.56.11s.93"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2000.71.4.521"},{"key":"e_1_2_7_7_1","first-page":"179","article-title":"The uptake and localization of tetracycline in human blood cells","volume":"51","author":"Park JK","year":"1970","journal-title":"Br J Exp Pathol"},{"key":"e_1_2_7_8_1","first-page":"233","article-title":"Kinetics of the uptake of antimicrobial agents by human polymorphonuclear leukocytes","volume":"39","author":"Laufen H","year":"1989","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_7_9_1","first-page":"39","article-title":"Fluxes and accumulation of tetracyclines by human blood cells","volume":"72","author":"Gabler WL","year":"1991","journal-title":"Res Commun Chem Pathol Pharmacol"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.11.2710"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.10.3345-3348.2003"},{"key":"e_1_2_7_12_1","first-page":"77","article-title":"Isolation of mononuclear cells and granulocytes from human blood. 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