{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:21:32Z","timestamp":1790112092097,"version":"4.0.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2010,8,1]],"date-time":"2010-08-01T00:00:00Z","timestamp":1280620800000},"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":[[2010,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Myeloid cells recruited to sites of bacterial inflammation are exposed to low oxygen tension, hypoxia, and high concentrations of inflammatory cytokines that significantly affect myeloid cell function. Therefore, we analyzed the direct consequences of acute and severe hypoxia on monocytic adhesion to the endothelium in coculture experiments. Marked upregulation of monocytic ICAM-1, but no other monocytic adhesion molecule, was responsible for an \u224850-fold increase in adhesion of the monocytic cells THP-1 to human and rat endothelial cells. ICAM-1 expression was rapidly induced after the onset of severe hypoxia, but it decreased after 4 h. Knockdown of ICAM-1 by siRNA in endothelial and monocytic cells abolished the adhesion, indicating that ICAM-1 expression on both cell types was indispensable for hypoxia-induced adhesion of monocytes to the endothelium. siRNA-mediated knockdown of hypoxia inducible factor (HIF)-1\u03b1, HIF-2\u03b1, and the NF-\u03baB family member p65 revealed that hypoxic upregulation of ICAM-1 resulted from hypoxic NF-\u03baB induction but not from activation of HIFs. Within the leukocyte-adhesion cascade, our results provide evidence for prolyl hydroxylase-dependent but HIF-independent activation of hypoxia-induced monocyte\u2013endothelial adhesion and assign a new function to monocytic ICAM-1 under acute hypoxic conditions.<\/jats:p>","DOI":"10.4049\/jimmunol.0903244","type":"journal-article","created":{"date-parts":[[2010,6,24]],"date-time":"2010-06-24T02:54:32Z","timestamp":1277348072000},"page":"1786-1793","source":"Crossref","is-referenced-by-count":68,"title":["Acute Hypoxia Induces HIF-Independent Monocyte Adhesion to Endothelial Cells through Increased Intercellular Adhesion Molecule-1 Expression: The Role of Hypoxic Inhibition of Prolyl Hydroxylase Activity for the Induction of NF-\u03baB"],"prefix":"10.1093","volume":"185","author":[{"given":"Sandra","family":"Winning","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Physiologie, Universit\u00e4t Duisburg-Essen , Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Splettstoesser","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Physiologie, Universit\u00e4t Duisburg-Essen , Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Fandrey","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Physiologie, Universit\u00e4t Duisburg-Essen , Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stilla","family":"Frede","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Physiologie, Universit\u00e4t Duisburg-Essen , Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,8,1]]},"reference":[{"key":"2025032411422137400_r1","doi-asserted-by":"crossref","first-page":"256","DOI":"10.4161\/cc.4.2.1407","article-title":"Inflammatory hypoxia: role of hypoxia-inducible factor","volume":"4","author":"Karhausen","year":"2005","journal-title":"Cell Cycle"},{"key":"2025032411422137400_r2","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s00424-005-1413-7","article-title":"Hypoxia-responsive transcription factors","volume":"450","author":"Cummins","year":"2005","journal-title":"Pflugers Arch."},{"key":"2025032411422137400_r3","first-page":"405","article-title":"Regulation of hypoxia-inducible factors during inflammation","volume":"435","author":"Frede","year":"2007","journal-title":"Methods Enzymol."},{"key":"2025032411422137400_r4","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1101\/gad.1881410","article-title":"Differential activation and antagonistic function of HIF-alpha isoforms in macrophages are essential for NO homeostasis","volume":"24","author":"Takeda","year":"2010","journal-title":"Genes Dev."},{"key":"2025032411422137400_r5","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/S0092-8674(03)00154-5","article-title":"HIF-1alpha is essential for myeloid cell-mediated inflammation","volume":"112","author":"Cramer","year":"2003","journal-title":"Cell"},{"key":"2025032411422137400_r6","doi-asserted-by":"crossref","first-page":"192","DOI":"10.4161\/cc.2.3.402","article-title":"A novel role for the hypoxia inducible transcription factor HIF-1alpha: critical regulation of inflammatory cell function","volume":"2","author":"Cramer","year":"2003","journal-title":"Cell Cycle"},{"key":"2025032411422137400_r7","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1172\/JCI25740","article-title":"HIF-1alpha: a master regulator of innate host defenses?","volume":"115","author":"Zarember","year":"2005","journal-title":"J. Clin. Invest."},{"key":"2025032411422137400_r8","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1007\/s00109-007-0282-2","article-title":"Hypoxia inducible factor (HIF) function in innate immunity and infection","volume":"85","author":"Zinkernagel","year":"2007","journal-title":"J. Mol. Med."},{"key":"2025032411422137400_r9","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/clinchem\/45.1.7","article-title":"New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases","volume":"45","author":"Chen","year":"1999","journal-title":"Clin. Chem."},{"key":"2025032411422137400_r10","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.cardiores.2006.05.005","article-title":"Regulating cellular oxygen sensing by hydroxylation","volume":"71","author":"Fandrey","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"2025032411422137400_r11","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1101\/gad.14.16.1983","article-title":"HIF-1 and human disease: one highly involved factor","volume":"14","author":"Semenza","year":"2000","journal-title":"Genes Dev."},{"key":"2025032411422137400_r12","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1242\/jcs.035022","article-title":"HIF at a glance","volume":"122","author":"Brahimi-Horn","year":"2009","journal-title":"J. Cell Sci."},{"key":"2025032411422137400_r13","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1042\/BJ20051839","article-title":"Bacterial lipopolysaccharide induces HIF-1 activation in human monocytes via p44\/42 MAPK and NF-kappaB","volume":"396","author":"Frede","year":"2006","journal-title":"Biochem. J."},{"key":"2025032411422137400_r14","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1042\/BJ20080920","article-title":"The cross-talk between NF-kappaB and HIF-1: further evidence for a significant liaison","volume":"412","author":"G\u00f6rlach","year":"2008","journal-title":"Biochem. J."},{"key":"2025032411422137400_r15","doi-asserted-by":"crossref","first-page":"6470","DOI":"10.4049\/jimmunol.0802378","article-title":"Hypoxia-inducible factor (HIF) 1\u03b1 accumulation and HIF target gene expression are impaired after induction of endotoxin tolerance","volume":"182","author":"Frede","year":"2009","journal-title":"J. Immunol."},{"key":"2025032411422137400_r16","doi-asserted-by":"crossref","first-page":"10440","DOI":"10.1073\/pnas.0401339101","article-title":"Leukocyte adhesion during hypoxia is mediated by HIF-1-dependent induction of \u03b22 integrin gene expression","volume":"101","author":"Kong","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032411422137400_r17","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.4049\/jimmunol.179.3.1934","article-title":"Identification of Pur \u03b1 as a new hypoxia response factor responsible for coordinated induction of the \u03b22 integrin family","volume":"179","author":"Kong","year":"2007","journal-title":"J. Immunol."},{"key":"2025032411422137400_r18","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1160\/TH07-02-0156","article-title":"Neutrophil activation via \u03b22 integrins (CD11\/CD18): molecular mechanisms and clinical implications","volume":"98","author":"Schymeinsky","year":"2007","journal-title":"Thromb. Haemost."},{"key":"2025032411422137400_r19","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1096\/fasebj.8.8.8181668","article-title":"Adhesion molecules and inflammatory injury","volume":"8","author":"Albelda","year":"1994","journal-title":"FASEB J."},{"key":"2025032411422137400_r20","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1083\/jcb.120.2.545","article-title":"A subpopulation of Mac-1 (CD11b\/CD18) molecules mediates neutrophil adhesion to ICAM-1 and fibrinogen","volume":"120","author":"Diamond","year":"1993","journal-title":"J. Cell Biol."},{"key":"2025032411422137400_r21","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.4049\/jimmunol.137.4.1270","article-title":"A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1","volume":"137","author":"Rothlein","year":"1986","journal-title":"J. Immunol."},{"key":"2025032411422137400_r22","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/sj.bjp.0702328","article-title":"Leukocyte-endothelial cell adhesion: avenues for therapeutic intervention","volume":"126","author":"Pan\u00e9s","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"2025032411422137400_r23","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nri2156","article-title":"Getting to the site of inflammation: the leukocyte adhesion cascade updated","volume":"7","author":"Ley","year":"2007","journal-title":"Nat. Rev. Immunol."},{"issue":"2","key":"2025032411422137400_r24","doi-asserted-by":"crossref","first-page":"S375","DOI":"10.1016\/j.jaci.2007.07.030","article-title":"3. Adhesion molecules and receptors","volume":"121","author":"Smith","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025032411422137400_r25","first-page":"365","article-title":"Mechanisms and consequences of leukocyte-endothelial interaction","volume":"155","author":"Harlan","year":"1991","journal-title":"West. J. Med."},{"key":"2025032411422137400_r26","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/nri1375","article-title":"Adhesion mechanisms regulating the migration of monocytes","volume":"4","author":"Imhof","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"2025032411422137400_r27","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1172\/JCI112200","article-title":"Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines","volume":"76","author":"Bevilacqua","year":"1985","journal-title":"J. Clin. Invest."},{"key":"2025032411422137400_r28","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1369\/jhc.6A7171.2007","article-title":"Effects of TNF-alpha on leukocyte adhesion molecule expressions in cultured human lymphatic endothelium","volume":"55","author":"Sawa","year":"2007","journal-title":"J. Histochem. Cytochem."},{"key":"2025032411422137400_r29","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1161\/01.ATV.0000147406.00871.b3","article-title":"Intracellular labile iron modulates adhesion of human monocytes to human endothelial cells","volume":"24","author":"Kartikasari","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2025032411422137400_r30","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0891-5849(92)90161-9","article-title":"Hypoxia\/reoxygenation stimulates endothelium to promote neutrophil adhesion","volume":"13","author":"Palluy","year":"1992","journal-title":"Free Radic. Biol. Med."},{"key":"2025032411422137400_r31","doi-asserted-by":"crossref","first-page":"C55","DOI":"10.1152\/ajpcell.00585.2003","article-title":"Signals mediating cleavage of intercellular adhesion molecule-1","volume":"287","author":"Tsakadze","year":"2004","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2025032411422137400_r32","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/346425a0","article-title":"Adhesion receptors of the immune system","volume":"346","author":"Springer","year":"1990","journal-title":"Nature"},{"key":"2025032411422137400_r33","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/0003-2697(87)90021-2","article-title":"Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction","volume":"162","author":"Chomczynski","year":"1987","journal-title":"Anal. Biochem."},{"key":"2025032411422137400_r34","doi-asserted-by":"crossref","first-page":"18154","DOI":"10.1073\/pnas.0602235103","article-title":"Prolyl hydroxylase-1 negatively regulates IkappaB kinase-\u03b2, giving insight into hypoxia-induced NFkappaB activity","volume":"103","author":"Cummins","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032411422137400_r35","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1089\/ars.2008.2400","article-title":"Hypoxia activates NF-kappaB-dependent gene expression through the canonical signaling pathway","volume":"11","author":"Oliver","year":"2009","journal-title":"Antioxid. Redox Signal."},{"key":"2025032411422137400_r36","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/0092-8674(91)90279-8","article-title":"Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity","volume":"67","author":"Butcher","year":"1991","journal-title":"Cell"},{"key":"2025032411422137400_r37","doi-asserted-by":"crossref","first-page":"H1980","DOI":"10.1152\/ajpheart.00322.2002","article-title":"Oxygen tension distribution in postcapillary venules in resting skeletal muscle","volume":"285","author":"Saltzman","year":"2003","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2025032411422137400_r38","doi-asserted-by":"crossref","first-page":"4055","DOI":"10.1113\/jphysiol.2008.157669","article-title":"Interdependent roles for hypoxia inducible factor and nuclear factor-kappaB in hypoxic inflammation","volume":"586","author":"Taylor","year":"2008","journal-title":"J. Physiol."},{"key":"2025032411422137400_r39","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1046\/j.1440-1681.1999.02992.x","article-title":"Endothelial cell responses to hypoxic stress","volume":"26","author":"Faller","year":"1999","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"2025032411422137400_r40","first-page":"1425","article-title":"Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues","volume":"54","author":"Koong","year":"1994","journal-title":"Cancer Res."},{"key":"2025032411422137400_r41","doi-asserted-by":"crossref","first-page":"3139","DOI":"10.1182\/blood-2008-12-172825","article-title":"Regulation of macrophage function in tumors: the multifaceted role of NF-kappaB","volume":"113","author":"Hagemann","year":"2009","journal-title":"Blood"},{"key":"2025032411422137400_r42","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S0171-2985(97)80026-5","article-title":"NF-kappa B\/Rel family members regulating the ICAM-1 promoter in monocytic THP-1 cells","volume":"198","author":"Wissink","year":"1997","journal-title":"Immunobiology"},{"key":"2025032411422137400_r43","first-page":"151","article-title":"Effect of activation of nuclear factor-KappaB on modulation of secretion of intercellular adhesion molecule-1 by A549 cell","volume":"21","author":"Liao","year":"2009","journal-title":"Zhongguo Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"2025032411422137400_r44","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1074\/jbc.270.2.933","article-title":"Transcriptional regulation of the intercellular adhesion molecule-1 gene by inflammatory cytokines in human endothelial cells. Essential roles of a variant NF-kappa B site and p65 homodimers","volume":"270","author":"Ledebur","year":"1995","journal-title":"J. Biol. Chem."},{"key":"2025032411422137400_r45","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1165\/ajrcmb.22.6.3925","article-title":"Effects of TNF-alpha on expression of ICAM-1 in human airway epithelial cells in vitro. Signaling pathways controlling surface and gene expression","volume":"22","author":"Krunkosky","year":"2000","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2025032411422137400_r46","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.ccr.2009.04.010","article-title":"Tumor vasculature is regulated by PHD2-mediated angiogenesis and bone marrow-derived cell recruitment","volume":"15","author":"Chan","year":"2009","journal-title":"Cancer Cell"},{"key":"2025032411422137400_r47","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1182\/blood.V84.7.2068.2068","article-title":"Leukocyte-endothelial adhesion molecules","volume":"84","author":"Carlos","year":"1994","journal-title":"Blood"},{"key":"2025032411422137400_r48","first-page":"737","article-title":"ICAM-1 and CD11b\/CD18 expression during acute pancreatitis induced by bile-pancreatic duct obstruction: effect of N-acetylcysteine","volume":"232","author":"Ramudo","year":"2007","journal-title":"Exp. Biol. Med. (Maywood)"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/185\/3\/1786\/61609109\/0903244.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/185\/3\/1786\/61609109\/0903244.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T22:12:04Z","timestamp":1743199924000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/185\/3\/1786\/7977530"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,8,1]]},"references-count":48,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2010,8,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0903244","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2010,8]]},"published":{"date-parts":[[2010,8,1]]}}}