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A novel recombinant antibody specific to full-length stromal derived factor-1 for potential application in biomarker studies

Bromage, DI; Taferner, S; Pillai, M; Yellon, DM; Davidson, SM; (2017) A novel recombinant antibody specific to full-length stromal derived factor-1 for potential application in biomarker studies. PLoS One , 12 (4) , Article e0174447. 10.1371/journal.pone.0174447. Green open access

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Abstract

Background: Stromal derived factor-1α (SDF-1α/CXCL12) is a chemokine that is up-regulated in diseases characterised by tissue hypoxia, including myocardial infarction, ischaemic cardiomyopathy and remote ischaemic conditioning (RIC), a technique of cyclical, non-injurious ischaemia applied remote from the heart that protects the heat from lethal ischaemia-reperfusion injury. Accordingly, there is considerable interest in SDF-1α as a potential biomarker of such conditions. However, SDF-1α is rapidly degraded and inactivated by dipeptidyl peptidase 4 and other peptidases, and the kinetics of intact SDF-1α remain unknown. Methods & results: To facilitate investigation of full-length SDF-1α we established an ELISA using a novel recombinant human antibody we developed called HCI.SDF1. HCI.SDF1 is specific to the N-terminal sequence of all isoforms of SDF-1 and has a comparable KD to commercially available antibodies. Together with a detection antibody specific to the α-isoform, HCI.SDF1 was used to specifically quantify full-length SDF-1α in blood for the first time. Using RIC applied to the hind limb of Sprague-Dawley rats or the arms of healthy human volunteers, we demonstrate an increase in SDF-1α using a commercially available antibody, as previously reported, but an unexpected decrease in full-length SDF-1α after RIC in both species. Conclusions: We report for the first time the development of a novel recombinant antibody specific to fulllength SDF-1. Applied to RIC, we demonstrate a significant decrease in SDF-1α that is at odds with the literature and suggests a need to investigate the kinetics of full-length SDF-1α in conditions characterised by tissue hypoxia.

Type: Article
Title: A novel recombinant antibody specific to full-length stromal derived factor-1 for potential application in biomarker studies
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0174447
Publisher version: http://doi.org/10.1371/journal.pone.0174447
Language: English
Additional information: Copyright: © 2017 Bromage et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Enzyme-linked immunoassays, Blood plasma, Platelets, Library screening, Myocardial infarction, Ischemia, Peptide libraries, Biomarkers
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: https://discovery.ucl.ac.uk/id/eprint/1552825
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