Abstract Number: OC 38.4
Meeting: ISTH 2022 Congress
Background: Deep vein thrombosis and its complication pulmonary embolism and is a major health problem with an average annual incidence rate of 104 to 183 per 100 000 person-years. After thrombus formation its resolution is essential to re-establish blood flow.
Aims: In this funded study (Austrian Science Fund (FWF)), we aim to analyse the effect of CD62P-mediated cell migration and activation on thrombus resolution post thrombus formation.
Methods: Thrombus formation was induced by inferior vena cava ligation and mice were treated after 1 day with a CD62P-blocking antibody or isotype. The thrombus and the surrounding vessel were extracted for immunohistochemistry or flow cytometry. Data were analysed by unpaired Student’s t-test or ANOVA.
Results: Localising neutrophils and macrophages in the thrombotic lesion revealed that they enter the thrombus and vessel wall from the caudal site. Neutrophils were predominantly present one day and monocytes/macrophages three days after vessel ligation. As leukocyte extravasation is promoted by endothelial and platelet CD62P, we blocked CD62P at day 1 after thrombus formation. This reduced aggregates between platelets and neutrophils or Ly6Chigh monocytes compared to isotype-treated controls, leading to diminished neutrophils and Ly6Chigh monocytes in the cranial thrombus part. Continuous observation of thrombus volume by ultrasound revealed an accelerated thrombus breakdown after blocking CD62P, confirmed by decreased thrombus weight and length. To identify CD62P-mediated effects on thrombus structure, we applied scanning electron microscopy and observed reduced fibrin density in thrombi of anti-CD62P-antibody-treated mice. Corresponding, we found reduced tissue factor expression associated with macrophages and reduced neutrophil activation after CD62P inhibition.
Conclusion(s): We propose a CD62P-mediated cross talk of vessel wall, platelets, monocytes and neutrophils resulting in activation of innate immune cells and increased tissue factor expression. This initial activation of immune cells strengthens the thrombus and delays subsequent resolution processes.
To cite this abstract in AMA style:Kral-Pointner J, Haider P, Szabo P, Kaun C, Brekalo M, Salzmann M, Schneider K, Bleichart S, Kiss A, Hengstenberg C, Brostjan C, Bergmeister H, Assinger A, Podesser B, Wojta J, Hohensinner P. Preventing CD62P-mediated leukocyte infiltration and activation enhances thrombus resolution in mice [abstract]. https://abstracts.isth.org/abstract/preventing-cd62p-mediated-leukocyte-infiltration-and-activation-enhances-thrombus-resolution-in-mice/. Accessed February 20, 2024.
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