Dataset Information

Ly6CLo Monocyte/Macrophages are Essential for Thrombus Resolution in a Murine Model of Venous Thrombosis.

ABSTRACT: Venous thrombosis (VT) resolution is a complex process, resembling sterile wound healing. Infiltrating blood-derived monocyte/macrophages (Mo/M?s) are essential for the regulation of inflammation in tissue repair. These cells differentiate into inflammatory (CD11b+Ly6CHi) or proreparative (CD11b+Ly6CLo) subtypes. Previous studies have shown that infiltrating Mo/M?s are important for VT resolution, but the precise roles of different Mo/M?s subsets are not well understood. Utilizing murine models of stasis and stenosis inferior vena cava thrombosis in concert with a Mo/M? depletion model (CD11b-diphtheria toxin receptor [DTR]-expressing mice), we examined the effect of Mo/M? depletion on thrombogenesis and VT resolution. In the setting of an 80 to 90% reduction in circulating CD11b+Mo/M?s, we demonstrated that Mo/M?s are not essential for thrombogenesis, with no difference in thrombus size, neutrophil recruitment, or neutrophil extracellular traps found. Conversely, CD11b+Mo/M? are essential for VT resolution. Diphtheria toxoid (DTx)-mediated depletion after thrombus creation depleted primarily CD11b+Ly6CLo Mo/M?s and resulted in larger thrombi. DTx-mediated depletion did not alter CD11b+Ly6CHi Mo/M? recruitment, suggesting a protective effect of CD11b+Ly6CLo Mo/M?s in VT resolution. Confirmatory Mo/M? depletion with clodronate lysosomes showed a similar phenotype, with failure to resolve VT. Adoptive transfer of CD11b+Ly6CLo Mo/M?s into Mo/M?-depleted mice reversed the phenotype, restoring normal thrombus resolution. These findings suggest that CD11b+Ly6CLo Mo/M?s are essential for normal VT resolution, consistent with the known proreparative function of this subset, and that further study of Mo/M? subsets may identify targets for immunomodulation to accelerate and improve thrombosis resolution.

SUBMITTER: Kimball AS

PROVIDER: S-EPMC7365023 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ly6CLo Monocyte/Macrophages are Essential for Thrombus Resolution in a Murine Model of Venous Thrombosis.

Kimball Andrew Scott AS Obi Andrea Tara AT Luke Catherine E CE Dowling Abigail R AR Cai Qing Q Adili Reheman R Jankowski Hannah H Schaller Matthew M Holinstadt Michael M Jaffer Farouc A FA Kunkel Steven L SL Gallagher Katherine A KA Henke Peter K PK

Thrombosis and haemostasis 20191230 2

Venous thrombosis (VT) resolution is a complex process, resembling sterile wound healing. Infiltrating blood-derived monocyte/macrophages (Mo/MΦs) are essential for the regulation of inflammation in tissue repair. These cells differentiate into inflammatory (CD11b+Ly6CHi) or proreparative (CD11b+Ly6CLo) subtypes. Previous studies have shown that infiltrating Mo/MΦs are important for VT resolution, but the precise roles of different Mo/MΦs subsets are n ...[more]

PMID: 31887775

Similar Datasets

Project description:BACKGROUND AND PURPOSE:The residual blood flow artifact is a critical confounder for MR black-blood thrombus imaging of cerebral venous sinus thrombosis. This study aimed to conduct a validation of a new MR black-blood thrombus imaging technique with enhanced blood signal suppression. MATERIALS AND METHODS:Twenty-six participants (13 volunteers and 13 patients) underwent conventional imaging methods followed by 2 randomized black-blood thrombus imaging scans, with a preoptimized delay alternating with nutation for tailored excitation (DANTE) preparation switched on and off, respectively. The signal intensity of residual blood, thrombus, brain parenchyma, normal lumen, and noise on black-blood thrombus images were measured. The thrombus volume, SNR of residual blood, and contrast-to-noise ratio for residual blood versus normal lumen, thrombus versus residual blood, and brain parenchyma versus normal lumen were compared between the 2 black-blood thrombus imaging techniques. Segmental diagnosis of venous sinus thrombosis was evaluated for each black-blood thrombus imaging technique using a combination of conventional imaging techniques as a reference. RESULTS:In the volunteer group, the SNR of residual blood (11.3 ± 2.9 versus 54.0 ± 23.4, P < .001) and residual blood-to-normal lumen contrast-to-noise ratio (7.5 ± 3.4 versus 49.2 ± 23.3, P < .001) were significantly reduced using the DANTE preparation. In the patient group, the SNR of residual blood (16.4 ± 8.0 versus 75.0 ± 35.1, P = .002) and residual blood-to-normal lumen contrast-to-noise ratio (12.4 ± 7.8 versus 68.8 ± 35.4, P = .002) were also significantly lower on DANTE-prepared black-blood thrombus imaging. The new black-blood thrombus imaging technique provided higher thrombus-to-residual blood contrast-to-noise ratio, significantly lower thrombus volume, and substantially improved diagnostic specificity and agreement with conventional imaging methods. CONCLUSIONS:DANTE-prepared black-blood thrombus imaging is a reliable MR imaging technique for diagnosing cerebral venous sinus thrombosis.

Dataset Information

Ly6CLo Monocyte/Macrophages are Essential for Thrombus Resolution in a Murine Model of Venous Thrombosis.

Publications

Ly6CLo Monocyte/Macrophages are Essential for Thrombus Resolution in a Murine Model of Venous Thrombosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets