Ligation of Glycophorin A Generates Reactive Oxygen Species Leading to Decreased Red Blood Cell Function.
Acute, 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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4718526?pdf=render |
| _version_ | 1819242740288847872 |
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| author | Joseph Khoory Jessica Estanislau Abdallah Elkhal Asmae Lazaar Mark I Melhorn Abigail Brodsky Ben Illigens Itaru Hamachi Yasutaka Kurishita Alexander R Ivanov Sergey Shevkoplyas Nathan I Shapiro Ionita C Ghiran |
| author_facet | Joseph Khoory Jessica Estanislau Abdallah Elkhal Asmae Lazaar Mark I Melhorn Abigail Brodsky Ben Illigens Itaru Hamachi Yasutaka Kurishita Alexander R Ivanov Sergey Shevkoplyas Nathan I Shapiro Ionita C Ghiran |
| author_sort | Joseph Khoory |
| collection | DOAJ |
| description | Acute, 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. |
| first_indexed | 2024-12-23T14:44:36Z |
| format | Article |
| id | doaj.art-b47bcf1e60d541088588fdea895e9ab2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T14:44:36Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b47bcf1e60d541088588fdea895e9ab22022-12-21T17:43:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014120610.1371/journal.pone.0141206Ligation of Glycophorin A Generates Reactive Oxygen Species Leading to Decreased Red Blood Cell Function.Joseph KhooryJessica EstanislauAbdallah ElkhalAsmae LazaarMark I MelhornAbigail BrodskyBen IlligensItaru HamachiYasutaka KurishitaAlexander R IvanovSergey ShevkoplyasNathan I ShapiroIonita C GhiranAcute, 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.http://europepmc.org/articles/PMC4718526?pdf=render |
| spellingShingle | Joseph Khoory Jessica Estanislau Abdallah Elkhal Asmae Lazaar Mark I Melhorn Abigail Brodsky Ben Illigens Itaru Hamachi Yasutaka Kurishita Alexander R Ivanov Sergey Shevkoplyas Nathan I Shapiro Ionita C Ghiran Ligation of Glycophorin A Generates Reactive Oxygen Species Leading to Decreased Red Blood Cell Function. PLoS ONE |
| title | Ligation of Glycophorin A Generates Reactive Oxygen Species Leading to Decreased Red Blood Cell Function. |
| title_full | Ligation of Glycophorin A Generates Reactive Oxygen Species Leading to Decreased Red Blood Cell Function. |
| title_fullStr | Ligation of Glycophorin A Generates Reactive Oxygen Species Leading to Decreased Red Blood Cell Function. |
| title_full_unstemmed | Ligation of Glycophorin A Generates Reactive Oxygen Species Leading to Decreased Red Blood Cell Function. |
| title_short | Ligation of Glycophorin A Generates Reactive Oxygen Species Leading to Decreased Red Blood Cell Function. |
| title_sort | ligation of glycophorin a generates reactive oxygen species leading to decreased red blood cell function |
| url | http://europepmc.org/articles/PMC4718526?pdf=render |
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