Ligation of Glycophorin A Generates Reactive Oxygen Species Leading to Decreased Red Blood Cell Function

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dc.contributor.authorKhoory, Joseph A.
dc.contributor.authorEstanislau, Jessica
dc.contributor.authorElkhal, Abdallah
dc.contributor.authorLazaar, Asmae
dc.contributor.authorMelhorn, Mark I.
dc.contributor.authorBrodsky, Abigail
dc.contributor.authorIlligens, Ben
dc.contributor.authorHamanchi, Itaru
dc.contributor.authorKurishita, Yasutaka
dc.contributor.authorIvanov, Alexander R.
dc.contributor.authorShevkoplyas, Sergey S.
dc.contributor.authorShapiro, Nathan I.
dc.contributor.authorGhiran, Ionita C.
dc.date.accessioned2020-03-10T19:51:14Z
dc.date.available2020-03-10T19:51:14Z
dc.date.issued1/19/2016
dc.description.abstractAcute, inflammatory conditions associated with dysregulated complement activation are characterized by significant increases in blood concentration of reactive oxygen species (ROS) and ATP. The mechanisms by which these molecules arise are not fully understood. In this study, using luminometric- and fluorescence-based methods, we show that ligation of glycophorin A (GPA) on human red blood cells (RBCs) results in a 2.1-fold, NADPH-oxidase-dependent increase in intracellular ROS that, in turn, trigger multiple downstream cascades leading to caspase-3 activation, ATP release, and increased band 3 phosphorylation. Functionally, using 2D microchannels to assess membrane deformability, GPS-ligated RBCs travel 33% slower than control RBCs, and lipid mobility was hindered by 10% using fluorescence recovery after photobleaching (FRAP). These outcomes were preventable by pretreating RBCs with cell-permeable ROS scavenger glutathione monoethyl ester (GSH-ME). Our results obtained in vitro using anti-GPA antibodies were validated using complement-altered RBCs isolated from control and septic patients. Our results suggest that during inflammatory conditions, circulating RBCs significantly contribute to capillary flow dysfunctions, and constitute an important but overlooked source of intravascular ROS and ATP, both critical mediators responsible for endothelial cell activation, microcirculation impairment, platelet activation, as well as long-term dysregulated adaptive and innate immune responses.
dc.identifier.citationCopyright 2016 PLoS. Recommended citation: Khoory, Joseph, Jessica Estanislau, Abdallah Elkhal, Asmae Lazaar, Mark I. Melhorn, Abigail Brodsky, Ben Illigens et al. "Ligation of glycophorin a generates reactive oxygen species leading to decreased red blood cell function." PLoS One 11, no. 1 (2016): e0141206. DOI: 10.1371/journal.pone.0141206 URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0141206&type=printable Reproduced in accordance with the original publisher’s licensing terms and with permission from the author(s).
dc.identifier.urihttps://hdl.handle.net/10657/6167
dc.language.isoen_US
dc.publisherPLoS One
dc.subjectSepsis
dc.subjectFlow cytometry
dc.subjectPhosphorylation
dc.subjectCell membranes
dc.subjectComplement system
dc.subjectLipids
dc.subjectInflammation
dc.subjectFlourescence recovery after photobleaching
dc.titleLigation of Glycophorin A Generates Reactive Oxygen Species Leading to Decreased Red Blood Cell Function
dc.typearticle

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