Platelet-Neutrophil Interactions and NET Formation in Severe Sepsis

Date
2013-01-10
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Abstract
Sepsis is a life threatening condition that accounts for a high mortality rate worldwide. Platelets and neutrophils are well recognized to interact in sepsis, however the molecules involved are not clear. Under non-septic conditions neutrophils can roll and adhere to immobilized platelets through a P-selectin/β2-integrin dependent mechanism. In contrast, in vivo imaging using models of sepsis and endotoxemia, indicates that neutrophils adhere to the endothelium first rather than platelets and then the platelets interact with immobilized neutrophils. LPS-activated platelets do not express P-selectin, thus, we hypothesized that platelets use different adhesion molecules to bind immobilized neutrophils in response to LPS. By using a flow chamber assay and LPS to mimic sepsis, we demonstrate that adhesion is mediated by LFA-1 and CD11c and the ligands JAM-A and ICAM-1. However septic plasma stimulation resulted in different adhesive pathways. We observed that the interaction was important for the NET formation presumably by allowing close proximity and transfer of mediators from the platelets to the neutrophil. We also observed that accumulation of platelet-derived mediator could directly induce NETs independent of adhesion.
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Keywords
Immunology
Citation
Urrutia, R. (2013). Platelet-Neutrophil Interactions and NET Formation in Severe Sepsis (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27368