Endothelial ACKR1 is induced by neutrophil contact and down-regulated by secretion in extracellular vesicles
Atypical chemokine receptor-1 (ACKR1), previously known as the Duffy antigen receptor for chemokines, is a widely conserved cell surface protein that is expressed on erythrocytes and the endothelium of post-capillary venules. In addition to being the receptor for the parasite causing malaria, ACKR1...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1181016/full |
| _version_ | 1797843257139396608 |
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| author | Xinying Guo Xinying Guo Negar Khosraviani Negar Khosraviani Sneha Raju Joshya Singh Nikki Zamani Farahani Madlene Abramian Victor J. Torres Kathryn L. Howe Jason E. Fish Jason E. Fish Andras Kapus Andras Kapus Warren L. Lee Warren L. Lee Warren L. Lee Warren L. Lee |
| author_facet | Xinying Guo Xinying Guo Negar Khosraviani Negar Khosraviani Sneha Raju Joshya Singh Nikki Zamani Farahani Madlene Abramian Victor J. Torres Kathryn L. Howe Jason E. Fish Jason E. Fish Andras Kapus Andras Kapus Warren L. Lee Warren L. Lee Warren L. Lee Warren L. Lee |
| author_sort | Xinying Guo |
| collection | DOAJ |
| description | Atypical chemokine receptor-1 (ACKR1), previously known as the Duffy antigen receptor for chemokines, is a widely conserved cell surface protein that is expressed on erythrocytes and the endothelium of post-capillary venules. In addition to being the receptor for the parasite causing malaria, ACKR1 has been postulated to regulate innate immunity by displaying and trafficking chemokines. Intriguingly, a common mutation in its promoter leads to loss of the erythrocyte protein but leaves endothelial expression unaffected. Study of endothelial ACKR1 has been limited by the rapid down-regulation of both transcript and protein when endothelial cells are extracted and cultured from tissue. Thus, to date the study of endothelial ACKR1 has been limited to heterologous over-expression models or the use of transgenic mice. Here we report that exposure to whole blood induces ACKR1 mRNA and protein expression in cultured primary human lung microvascular endothelial cells. We found that contact with neutrophils is required for this effect. We show that NF-κB regulates ACKR1 expression and that upon removal of blood, the protein is rapidly secreted by extracellular vesicles. Finally, we confirm that endogenous ACKR1 does not signal upon stimulation with IL-8 or CXCL1. Our observations define a simple method for inducing endogenous endothelial ACKR1 protein that will facilitate further functional studies. |
| first_indexed | 2024-04-09T17:02:14Z |
| format | Article |
| id | doaj.art-974cee610b824e988de4bbf118efaf78 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T17:02:14Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-974cee610b824e988de4bbf118efaf782023-04-21T04:31:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11810161181016Endothelial ACKR1 is induced by neutrophil contact and down-regulated by secretion in extracellular vesiclesXinying Guo0Xinying Guo1Negar Khosraviani2Negar Khosraviani3Sneha Raju4Joshya Singh5Nikki Zamani Farahani6Madlene Abramian7Victor J. Torres8Kathryn L. Howe9Jason E. Fish10Jason E. Fish11Andras Kapus12Andras Kapus13Warren L. Lee14Warren L. Lee15Warren L. Lee16Warren L. Lee17Keenan Centre for Biomedical Research, St. Michael’s Hospital, Toronto, ON, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaKeenan Centre for Biomedical Research, St. Michael’s Hospital, Toronto, ON, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaToronto General Hospital Research Institute, University Health Network, Toronto, ON, CanadaKeenan Centre for Biomedical Research, St. Michael’s Hospital, Toronto, ON, CanadaKeenan Centre for Biomedical Research, St. Michael’s Hospital, Toronto, ON, CanadaKeenan Centre for Biomedical Research, St. Michael’s Hospital, Toronto, ON, CanadaDepartment of Microbiology, New York University Grossman School of Medicine, New York, NY, United StatesToronto General Hospital Research Institute, University Health Network, Toronto, ON, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaToronto General Hospital Research Institute, University Health Network, Toronto, ON, CanadaKeenan Centre for Biomedical Research, St. Michael’s Hospital, Toronto, ON, CanadaDepartment of Biochemistry, University of Toronto, Toronto, ON, CanadaKeenan Centre for Biomedical Research, St. Michael’s Hospital, Toronto, ON, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaDepartment of Biochemistry, University of Toronto, Toronto, ON, CanadaDepartment of Medicine and the Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, CanadaAtypical chemokine receptor-1 (ACKR1), previously known as the Duffy antigen receptor for chemokines, is a widely conserved cell surface protein that is expressed on erythrocytes and the endothelium of post-capillary venules. In addition to being the receptor for the parasite causing malaria, ACKR1 has been postulated to regulate innate immunity by displaying and trafficking chemokines. Intriguingly, a common mutation in its promoter leads to loss of the erythrocyte protein but leaves endothelial expression unaffected. Study of endothelial ACKR1 has been limited by the rapid down-regulation of both transcript and protein when endothelial cells are extracted and cultured from tissue. Thus, to date the study of endothelial ACKR1 has been limited to heterologous over-expression models or the use of transgenic mice. Here we report that exposure to whole blood induces ACKR1 mRNA and protein expression in cultured primary human lung microvascular endothelial cells. We found that contact with neutrophils is required for this effect. We show that NF-κB regulates ACKR1 expression and that upon removal of blood, the protein is rapidly secreted by extracellular vesicles. Finally, we confirm that endogenous ACKR1 does not signal upon stimulation with IL-8 or CXCL1. Our observations define a simple method for inducing endogenous endothelial ACKR1 protein that will facilitate further functional studies.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1181016/fullatypical chemokine receptor 1Duffy antigenendotheliumneutrophilextracellular vesiclesleukocidin |
| spellingShingle | Xinying Guo Xinying Guo Negar Khosraviani Negar Khosraviani Sneha Raju Joshya Singh Nikki Zamani Farahani Madlene Abramian Victor J. Torres Kathryn L. Howe Jason E. Fish Jason E. Fish Andras Kapus Andras Kapus Warren L. Lee Warren L. Lee Warren L. Lee Warren L. Lee Endothelial ACKR1 is induced by neutrophil contact and down-regulated by secretion in extracellular vesicles Frontiers in Immunology atypical chemokine receptor 1 Duffy antigen endothelium neutrophil extracellular vesicles leukocidin |
| title | Endothelial ACKR1 is induced by neutrophil contact and down-regulated by secretion in extracellular vesicles |
| title_full | Endothelial ACKR1 is induced by neutrophil contact and down-regulated by secretion in extracellular vesicles |
| title_fullStr | Endothelial ACKR1 is induced by neutrophil contact and down-regulated by secretion in extracellular vesicles |
| title_full_unstemmed | Endothelial ACKR1 is induced by neutrophil contact and down-regulated by secretion in extracellular vesicles |
| title_short | Endothelial ACKR1 is induced by neutrophil contact and down-regulated by secretion in extracellular vesicles |
| title_sort | endothelial ackr1 is induced by neutrophil contact and down regulated by secretion in extracellular vesicles |
| topic | atypical chemokine receptor 1 Duffy antigen endothelium neutrophil extracellular vesicles leukocidin |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1181016/full |
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