Interactions between platelets and platelet derived microvesicles in inflamation

Box, Clare Louise (2015). Interactions between platelets and platelet derived microvesicles in inflamation. University of Birmingham. Ph.D.

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Abstract

Atherosclerosis is a chronic inflammatory disease, characterised by infiltration of leukocytes and accumulation of fatty deposits in the artery wall. Early events in this disease process include recruitment of platelets to the artery wall, which in turn aid in leukocyte recruitment. However, upon activation platelets release microvesicles (PMV), we are interested in whether PMV have a role in enhancing leukocyte recruitment.

We demonstrated using whole blood that upon activation, platelets form aggregates with monocytes and neutrophils. The data suggests that upon platelet activation, PMV may be generated and subsequently may have a role in heterotypic aggregate formation observed. Interestingly, lymphocytes did not form aggregates with platelets (or PMV) as readily. We showed that blocking P-selectin leads to a significant reduction in heterotypic aggregate formation. We also demonstrated the presence of P-selectin glycoprotein ligand-1 (PSGL 1), the ligand with the highest binding affinity for P-selectin, on monocytes and neutrophils.

Monocytes preferentially bound platelets or PMV. However, we found no significant increase in recruitment of these heterotypic aggregates to von Willebrand factor, under conditions of low shear stress compared to monocytes alone. These heterotypic aggregates provide a mechanism for cross-talk between cell types and have a potential role in inflammatory and thrombotic diseases.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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