Role of Monocytes and Neutrophils in Thrombosis
type: CreativeWork
description: Arterial thrombosis is the major trigger of myocardial infarction and ischaemic stroke. Although platelets are the most abundant cell in arterial thrombi, platelets interact closely with leukocytes such as monocytes and neutrophils and modify their activity. This thesis aims to identify novel mechanisms through which leukocytes and platelet-leukocyte interactions might contribute to thrombosis. The thesis focused on rapid interactions between these cells (on the order of minutes) as these interactions might contribute to initiation of thrombosis. Experimental methods used include microplate-based assays and flow cytometry. Firstly, physical interactions between platelets and leukocytes were studied via flow cytometry following whole blood stimulation with multiple platelet agonists. This identified monocytes and neutrophils as the major leukocyte subtypes to which activated platelets rapidly adhere regardless of the agonist used. Secondly, it was found that activated platelets adhering to monocytes caused the monocytes to rapidly expose on their surface tissue factor, a potent activator of the blood coagulation cascade. Previously reported to take hours, it was instead found that this process could occur on a timescale as short as five minutes, which, if active, might lead to rapid thrombus growth. Whole blood as well as isolated platelets and monocytes were used to study the mechanisms involved and the interaction between platelet P-selectin and its receptor PSGL-1 found on monocytes was identified as both necessary and sufficient to induce this event. The process was successfully inhibited with P-selectin and PSGL-1 blocking antibodies and could be induced in isolated monocytes by the addition of P-selectin-coated beads. Finally, the involvement of monocytes and neutrophils in the generation of the potent procoagulant enzyme thrombin was studied. Using a modified thrombin generation assay, it was found that monocytes do not contribute to the activation of thrombin…
abstract: Arterial thrombosis is the major trigger of myocardial infarction and ischaemic stroke. Although platelets are the most abundant cell in arterial thrombi, platelets interact closely with leukocytes such as monocytes and neutrophils and modify their activity. This thesis aims to identify novel mechanisms through which leukocytes and platelet-leukocyte interactions might contribute to thrombosis. The thesis focused on rapid interactions between these cells (on the order of minutes) as these interactions might contribute to initiation of thrombosis. Experimental methods used include microplate-based assays and flow cytometry. Firstly, physical interactions between platelets and leukocytes were studied via flow cytometry following whole blood stimulation with multiple platelet agonists. This identified monocytes and neutrophils as the major leukocyte subtypes to which activated platelets rapidly adhere regardless of the agonist used. Secondly, it was found that activated platelets adhering to monocytes caused the monocytes to rapidly expose on their surface tissue factor, a potent activator of the blood coagulation cascade. Previously reported to take hours, it was instead found that this process could occur on a timescale as short as five minutes, which, if active, might lead to rapid thrombus growth. Whole blood as well as isolated platelets and monocytes were used to study the mechanisms involved and the interaction between platelet P-selectin and its receptor PSGL-1 found on monocytes was identified as both necessary and sufficient to induce this event. The process was successfully inhibited with P-selectin and PSGL-1 blocking antibodies and could be induced in isolated monocytes by the addition of P-selectin-coated beads. Finally, the involvement of monocytes and neutrophils in the generation of the potent procoagulant enzyme thrombin was studied. Using a modified thrombin generation assay, it was found that monocytes do not contribute to the activation of thrombin…
author: Ivanov, Ivelin
language: eng
keywords: platelets, monocytes, neutrophils, thrombosis
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/1463c6da-26cd-4918-82de-37acef4d80b1/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2020-12-22
date modified: 2026-07-22T22:24:32Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.69595