ROS producing immature neutrophils in Giant Cell Arteritis are linked to vascular pathologies
Giant cell arteritis (GCA) is a common form of primary systemic vasculitis in adults with no reliable indicators of prognosis or treatment responses. We used single cell technologies to comprehensively map immune cell populations in the blood of patients with GCA and identified the CD66b+CD15+CD10lo...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2020
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| _version_ | 1797065549263405056 |
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| author | Wang, L Ai, Z Khoyratty, TE Zec, K Eames, HL van Grinsven, E Hudak, A Morris, S Ahern, DJ Monaco, C Eruslanov, EB Luqmani, R Udalova, IA |
| author_facet | Wang, L Ai, Z Khoyratty, TE Zec, K Eames, HL van Grinsven, E Hudak, A Morris, S Ahern, DJ Monaco, C Eruslanov, EB Luqmani, R Udalova, IA |
| author_sort | Wang, L |
| collection | OXFORD |
| description | Giant cell arteritis (GCA) is a common form of primary systemic vasculitis in adults with no reliable indicators of prognosis or treatment responses. We used single cell technologies to comprehensively map immune cell populations in the blood of patients with GCA and identified the CD66b+CD15+CD10lo/-CD64- band neutrophils and CD66bhiCD15+CD10lo/-CD64+/bright myelocytes/metamyelocytes to be unequivocally associated with both the clinical phenotype and response to treatment. Immature neutrophils were resistant to apoptosis, remained in the vasculature for a prolonged time, interacted with platelets, and extravasated into the tissue surrounding the temporal arteries of patients with GCA. We discovered that immature neutrophils generated high levels of extracellular reactive oxygen species, leading to enhanced protein oxidation and permeability of endothelial barrier in an in vitro co-culture system. The same populations were also detected in other systemic vasculitides. These findings link functions of immature neutrophils to disease pathogenesis, establishing a new clinical cellular signature of GCA and suggesting new therapeutic approaches in systemic vascular inflammation. |
| first_indexed | 2024-03-06T21:30:12Z |
| format | Journal article |
| id | oxford-uuid:4470adf5-e26a-48f4-8eec-060e7534e225 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:30:12Z |
| publishDate | 2020 |
| publisher | American Society for Clinical Investigation |
| record_format | dspace |
| spelling | oxford-uuid:4470adf5-e26a-48f4-8eec-060e7534e2252022-03-26T15:01:33ZROS producing immature neutrophils in Giant Cell Arteritis are linked to vascular pathologiesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4470adf5-e26a-48f4-8eec-060e7534e225EnglishSymplectic ElementsAmerican Society for Clinical Investigation2020Wang, LAi, ZKhoyratty, TEZec, KEames, HLvan Grinsven, EHudak, AMorris, SAhern, DJMonaco, CEruslanov, EBLuqmani, RUdalova, IAGiant cell arteritis (GCA) is a common form of primary systemic vasculitis in adults with no reliable indicators of prognosis or treatment responses. We used single cell technologies to comprehensively map immune cell populations in the blood of patients with GCA and identified the CD66b+CD15+CD10lo/-CD64- band neutrophils and CD66bhiCD15+CD10lo/-CD64+/bright myelocytes/metamyelocytes to be unequivocally associated with both the clinical phenotype and response to treatment. Immature neutrophils were resistant to apoptosis, remained in the vasculature for a prolonged time, interacted with platelets, and extravasated into the tissue surrounding the temporal arteries of patients with GCA. We discovered that immature neutrophils generated high levels of extracellular reactive oxygen species, leading to enhanced protein oxidation and permeability of endothelial barrier in an in vitro co-culture system. The same populations were also detected in other systemic vasculitides. These findings link functions of immature neutrophils to disease pathogenesis, establishing a new clinical cellular signature of GCA and suggesting new therapeutic approaches in systemic vascular inflammation. |
| spellingShingle | Wang, L Ai, Z Khoyratty, TE Zec, K Eames, HL van Grinsven, E Hudak, A Morris, S Ahern, DJ Monaco, C Eruslanov, EB Luqmani, R Udalova, IA ROS producing immature neutrophils in Giant Cell Arteritis are linked to vascular pathologies |
| title | ROS producing immature neutrophils in Giant Cell Arteritis are linked to vascular pathologies |
| title_full | ROS producing immature neutrophils in Giant Cell Arteritis are linked to vascular pathologies |
| title_fullStr | ROS producing immature neutrophils in Giant Cell Arteritis are linked to vascular pathologies |
| title_full_unstemmed | ROS producing immature neutrophils in Giant Cell Arteritis are linked to vascular pathologies |
| title_short | ROS producing immature neutrophils in Giant Cell Arteritis are linked to vascular pathologies |
| title_sort | ros producing immature neutrophils in giant cell arteritis are linked to vascular pathologies |
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