{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T18:26:03Z","timestamp":1761675963196},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[1999,1,22]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014Exposing human umbilical vein endothelial cells (HUVECs) to anoxia\/reoxygenation (A\/R) results in an increase in polymorphonuclear leukocyte (PMN) adhesion to HUVECs. This A\/R-induced hyperadhesion is completely prevented by a previous (24 hours earlier) exposure of HUVECs to A\/R. This phenomenon has been termed \u201cA\/R tolerance.\u201d Exposing HUVECs to A\/R induces an increase in nuclear factor \u03baB (NF-\u03baB) in HUVEC nuclei within 4 hours. Interfering with either NF-\u03baB activation (proteasome inhibitor) or translocation (double-stranded oligonucleotides containing NF-\u03baB binding sequence) prevents the development of A\/R tolerance (ie, the increase in A\/R-induced PMN adhesion to HUVECs is the same after the first and second A\/R challenges). NO production by HUVECs is increased after the second A\/R challenge, but not after the first A\/R challenge. Inhibition of NO synthase (NOS) during the second A\/R challenge prevents the development of A\/R tolerance with respect to PMN adhesion. However, while HUVECs contained endothelial NOS protein, no inducible NOS was detected in either tolerant or nontolerant cells. Further studies indicated that inhibition of GTP-cyclohydrolase I (an enzyme involved in de novo synthesis of an important cofactor for NOS activity, tetrahydrobiopterin) prevented the generation of NO in A\/R-tolerant cells. Extracellular generation of NO (NO donor) did not effect the hyperadhesion response induced by the initial A\/R challenge. A\/R also induced an oxidant stress in naive HUVECs, but not in A\/R-tolerant HUVECs. Inhibition of NOS during the second A\/R insult results in the generation of an oxidant stress similar to that observed after the first A\/R challenge. Taken together, the findings of the present study are consistent with a role for NF-\u03baB in the development of A\/R tolerance (with respect to PMN adhesion), perhaps by transcriptional regulation of GTP-cyclohydrolase. The increased NO production during the second A\/R insult reduces PMN adhesion most likely by reducing the intracellular oxidant stress induced by A\/R.\n          <\/jats:p>","DOI":"10.1161\/01.res.84.1.103","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"103-112","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["Anoxia\/Reoxygenation-Induced Tolerance With Respect to Polymorphonuclear Leukocyte Adhesion to Cultured Endothelial Cells"],"prefix":"10.1161","volume":"84","author":[{"given":"Gediminas","family":"Cepinskas","sequence":"first","affiliation":[{"name":"From the Vascular Cell Biology Laboratory, London Health Sciences Centre-Research Inc, London, Ontario, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cameron W.","family":"Lush","sequence":"additional","affiliation":[{"name":"From the Vascular Cell Biology Laboratory, London Health Sciences Centre-Research Inc, London, Ontario, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter R.","family":"Kvietys","sequence":"additional","affiliation":[{"name":"From the Vascular Cell Biology Laboratory, London Health Sciences Centre-Research Inc, London, Ontario, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1997.273.1.C1"},{"key":"e_1_3_2_2_2","unstructured":"Kvietys PR Cepinskas G Granger DN. Neutrophil-endothelial cell interactions during ischemia\/reperfusion. In: Kamada T Shiga T McCuskey RS eds. Tissue Perfusion and Organ Function: Ischemia\/Reperfusion Injury. Amsterdam the Netherlands: Elsevier; 1996:179\u2013191."},{"key":"e_1_3_2_3_2","first-page":"H1891","volume":"262","year":"1992","unstructured":"Yoshida N, Granger DN, Anderson DC, Rothlein R, Lane C, Kvietys PR. Anoxia\/reoxygenation-induced neutrophil adherence to cultured endothelial cells. Am J Physiol. 1992;262:H1891\u2013H1898.","journal-title":"Am J Physiol"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.81.6.922"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2828(95)90071-3"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1996.tb33510.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1990.197"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91596-S"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117541"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1993.264.3.C715"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.81.4.618"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.10.6089"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1993.tb05850.x"},{"key":"e_1_3_2_14_2","first-page":"84","volume":"7","year":"1997","unstructured":"Grisham MB, Johnson GG, Gautreaux MD, Berg RD. Measurement of nitrate and nitrite in extracellular fluids: a window to systemic nitric oxide metabolism. Methods: Companion Methods Enzymol. 1997;7:84\u201390.","journal-title":"Methods: Companion Methods Enzymol"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1993.1222"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2237444"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90030-6"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.10.110194.002201"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90506-5"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(96)00118-6"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117221"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)53931-4"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1994.266.2.C455"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.1.40"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47160-8"},{"key":"e_1_3_2_26_2","first-page":"499","volume":"68","year":"1993","unstructured":"Collins T. Biology of disease: endothelial nuclear factor-\u03baB and the initiation of the atherosclerotic lesion. Lab Invest. 1993;68:499\u2013508.","journal-title":"Lab Invest"},{"key":"e_1_3_2_27_2","first-page":"655","volume":"236","year":"1998","unstructured":"Kim YM, Lee BS, Yi KY, Paik SG. Upstream NF-kappa B site is required for the maximal expression of mouse inducible nitric oxide synthase gene in interferon-gamma plus lipopolysaccharide-induced RAW 264.7 macrophages. Biochem Biophys Res Commun. 1998;236:655\u2013660.","journal-title":"Biochem Biophys Res Commun"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118181"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199705)171:2<205::AID-JCP11>3.0.CO;2-C"},{"key":"e_1_3_2_30_2","first-page":"L643","volume":"270","year":"1996","unstructured":"North AJ, Lau KS, Brannon TS, Wu LC, Wells LB, German Z, Shaul PW. Oxygen upregulates nitric oxide synthase gene expression in ovine fetal pulmonary artery endothelial cells. Am J Physiol. 1996;270:L643\u2013L649.","journal-title":"Am J Physiol"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.2184"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42066-2"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(95)00886-1"},{"key":"e_1_3_2_34_2","first-page":"H665","volume":"273","year":"1997","unstructured":"Kasai K, Hattori Y, Banba N, Hattori S, Motohashi S, Shimoda S-I, Nakanishi N, Gross SS. Induction of tetrahydrobiopterin synthesis in rat cardiac myocytes: impact on cytokine-induced NO generation. Am J Physiol. 1997;273:H665\u2013H672.","journal-title":"Am J Physiol"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.RES.84.1.103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T20:48:09Z","timestamp":1715546889000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.RES.84.1.103"}},"subtitle":["A Nuclear Factor-\u03baB\u2013Mediated Phenomenon"],"short-title":[],"issued":{"date-parts":[[1999,1,22]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1999,1,22]]}},"alternative-id":["10.1161\/01.RES.84.1.103"],"URL":"https:\/\/doi.org\/10.1161\/01.res.84.1.103","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,1,22]]},"assertion":[{"value":"1998-06-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-10-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-01-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}