In situ visualization of endothelial cell-derived extracellular vesicle formation in steady state and malignant conditions

Atkin-Smith, GK; Santavanond, JP; Light, A; Rimes, JS; Samson, AL; Er, J; Liu, J; Johnson, DN; Le Page, M; Rajasekhar, P; Yip, RKH; Geoghegan, ND; Rogers, KL; Chang, C; Bryant, VL; Margetts, M; Keightley, MC; Kilpatrick, TJ; Binder, MD; Tran, S; Lee, EF; Fairlie, WD; Ozkocak, DC; Wei, AH; Hawkins, ED; Poon, IKH

Author(s): Atkin-Smith, GK; Santavanond, JP; Light, A; Rimes, JS; Samson, AL; Er, J; Liu, J; Johnson, DN; Le Page, M; Rajasekhar, P; Yip, RKH; Geoghegan, ND; Rogers, KL; Chang, C; Bryant, VL; Margetts, M; Keightley, MC; Kilpatrick, TJ; Binder, MD; Tran, S; Lee, EF; Fairlie, WD; Ozkocak, DC; Wei, AH; Hawkins, ED; Poon, IKH;
Details: Publication Year 2024-10-22,Volume 15,Issue #1,Page 8802
Journal Title: Nature Communications
Abstract: Endothelial cells are integral components of all vasculature within complex organisms. As they line the blood vessel wall, endothelial cells are constantly exposed to a variety of molecular factors and shear force that can induce cellular damage and stress. However, how endothelial cells are removed or eliminate unwanted cellular contents, remains unclear. The generation of large extracellular vesicles (EVs) has emerged as a key mechanism for the removal of cellular waste from cells that are dying or stressed. Here, we used intravital microscopy of the bone marrow to directly measure the kinetics of EV formation from endothelial cells in vivo under homoeostatic and malignant conditions. These large EVs are mitochondria-rich, expose the 'eat me' signal phosphatidylserine, and can interact with immune cell populations as a potential clearance mechanism. Elevated levels of circulating EVs correlates with degradation of the bone marrow vasculature caused by acute myeloid leukaemia. Together, our study provides in vivo spatio-temporal characterization of EV formation in the murine vasculature and suggests that circulating, large endothelial cell-derived EVs can provide a snapshot of vascular damage at distal sites.
Publisher: Springer Nature
Keywords: Animals; *Extracellular Vesicles/metabolism; *Endothelial Cells/metabolism; Mice; *Leukemia, Myeloid, Acute/metabolism/pathology; *Mice, Inbred C57BL; Bone Marrow/metabolism; Humans; Intravital Microscopy/methods; Phosphatidylserines/metabolism; Mitochondria/metabolism; Male; Female
Research Division(s): Inflammation; Advanced Technology and Biology; Infectious Diseases and Immune Defence; Immunology; Blood Cells and Blood Cancer
PubMed ID: 39438460
Publisher's Version: https://doi.org/10.1038/s41467-024-52867-5
Open Access at Publisher's Site: https://doi.org/ 10.1038/s41467-024-52867-5
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-10-25 10:49:20

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