{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:57:07Z","timestamp":1792663027821,"version":"4.5.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2016,5,17]],"date-time":"2016-05-17T00:00:00Z","timestamp":1463443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. National Institutes of Health","doi-asserted-by":"publisher","award":["HL111552"],"award-info":[{"award-number":["HL111552"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. National Institutes of Health","doi-asserted-by":"publisher","award":["GM114359"],"award-info":[{"award-number":["GM114359"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011781","name":"Shriners Hospitals for Children","doi-asserted-by":"publisher","award":["86400"],"award-info":[{"award-number":["86400"]}],"id":[{"id":"10.13039\/100011781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>A key step in neutrophil-mediated tissue damage is the migration of activated neutrophils across the vascular endothelium. Previously, we identified protein kinase C \u03b4 as a critical regulator of neutrophil migration in sepsis but did not identify specific steps in migration. In this study, we used our novel biomimetic microfluidic assay to delineate systematically the mechanism by which protein kinase C \u03b4 regulates individual steps in human neutrophil\u2013endothelial interaction during inflammation. The biomimetic microfluidic assay includes a network of vascular channels, produced from in vivo images connected to a tissue compartment through a porous barrier. HUVECs cultured in vascular channels formed a complete lumen under physiologic shear flow. HUVECs were pretreated with TNF-\u03b1 \u00b1 a protein kinase C \u03b4 inhibitor, and the tissue compartment was filled with a chemoattractant (fMLP or IL-8). Under physiologic shear flow, the role of protein kinase C \u03b4 on spatial and temporal neutrophil adherence\/migration was quantified. Protein kinase C \u03b4 inhibition significantly reduced neutrophil adhesion in response to fMLP and IL-8 only under low shear rate and near bifurcations. Protein kinase C \u03b4 inhibition also decreased adherence to nonactivated HUVECs in response to fMLP or IL-8. Protein kinase C \u03b4 inhibition reduced neutrophil migration into the tissue compartment in response to fMLP and to a lesser degree, to IL-8. Antibody-coated microparticles demonstrated that protein kinase C \u03b4 inhibition down-regulated E-selectin and ICAM-1 but not VCAM-1 expression. With the use of a physiologically relevant in vitro model system, we demonstrate that protein kinase C \u03b4 plays an important role in the regulation of neutrophil adherence\/migration during inflammation and identifies key steps regulated by protein kinase C \u03b4 in neutrophil\u2013endothelial interactions.<\/jats:p>","DOI":"10.1189\/jlb.3ma0216-087r","type":"journal-article","created":{"date-parts":[[2016,5,18]],"date-time":"2016-05-18T03:50:01Z","timestamp":1463543401000},"page":"1027-1035","source":"Crossref","is-referenced-by-count":35,"title":["A novel microfluidic assay reveals a key role for protein kinase C \u03b4 in regulating human neutrophil\u2013endothelium interaction"],"prefix":"10.1093","volume":"100","author":[{"given":"Fariborz","family":"Soroush","sequence":"first","affiliation":[{"name":"Department of Mechanical Engineering, College of Engineering, Temple University , Philadelphia, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Center for Inflammation, Clinical and Translational Lung Research, Lewis Katz School of Medicine at Temple University , Philadelphia, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devon J","family":"King","sequence":"additional","affiliation":[{"name":"Department of Physiology and Center for Inflammation, Clinical and Translational Lung Research, Lewis Katz School of Medicine at Temple University , Philadelphia, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, College of Engineering, Temple University , Philadelphia, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhir","family":"Deosarkar","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, College of Engineering, Temple University , Philadelphia, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balabhaskar","family":"Prabhakarpandian","sequence":"additional","affiliation":[{"name":"Biomedical Technology, CFD Research Corporation , Huntsville, Alabama , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie E","family":"Kilpatrick","sequence":"additional","affiliation":[{"name":"Department of Physiology and Center for Inflammation, Clinical and Translational Lung Research, Lewis Katz School of Medicine at Temple University , Philadelphia, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad F","family":"Kiani","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, College of Engineering, Temple University , Philadelphia, Pennsylvania , USA"},{"name":"Shriners Hospitals Pediatric Research Center, Temple University School of Medicine , Philadelphia, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,5,17]]},"reference":[{"issue":"7: Suppl","key":"2023011710430237200_B1","doi-asserted-by":"crossref","first-page":"S109","DOI":"10.1097\/00003246-200107001-00035","article-title":"Epidemiology of sepsis: an update","volume":"29","author":"Angus","year":"2001","journal-title":"Crit. 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