Endothelial ACKR1 is induced by neutrophil contact and down-regulated by secretion in extracellular vesicles

Frontiers in Immunology

Immunology

Jason E. Fish¹  Victor J. Torres²  Nikki Zamani Farahani³  Madlene Abramian³  Joshya Singh³  Andras Kapus⁴  Negar Khosraviani⁵  Xinying Guo⁵  Warren L. Lee⁶  Sneha Raju⁷  Kathryn L. Howe⁷ 

[1] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada;Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada;Department of Microbiology, New York University Grossman School of Medicine, New York, NY, United States;Keenan Centre for Biomedical Research, St. Michael’s Hospital, Toronto, ON, Canada;Keenan Centre for Biomedical Research, St. Michael’s Hospital, Toronto, ON, Canada;Department of Biochemistry, University of Toronto, Toronto, ON, Canada;Keenan Centre for Biomedical Research, St. Michael’s Hospital, Toronto, ON, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada;Keenan Centre for Biomedical Research, St. Michael’s Hospital, Toronto, ON, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada;Department of Biochemistry, University of Toronto, Toronto, ON, Canada;Department of Medicine and the Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada;Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada;

关键词: atypical chemokine receptor 1;    Duffy antigen;    endothelium;    neutrophil;    extracellular vesicles;    leukocidin;   

DOI  :  10.3389/fimmu.2023.1181016

 received in 2023-03-06, accepted in 2023-04-11,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Guo, Khosraviani, Raju, Singh, Farahani, Abramian, Torres, Howe, Fish, Kapus and Lee