The role of platelets in lymphocyte recruitment during liver inflamation

Robinson, Joseph (2016). The role of platelets in lymphocyte recruitment during liver inflamation. University of Birmingham. Ph.D.

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Abstract

Platelets have long been known to be capable of mediating lymphocyte recruitment. However, their role in recruitment of lymphocytes to the inflamed liver remains unclear. This was investigated in vivo in two murine models of hepatic injury: ischaemia reperfusion (IR) and concanavalin A (ConA) injury. Intravital microscopy studies were conducted in normal or thrombocytopenic mice undergoing sham surgery or injury. Hepatic recruitment of fluorescently labelled donor spleen derived T- and B-cells or donor platelets was determined. Platelet adhesion was observed in healthy and injured livers, but was not increased following injury when the whole region viewed microscopically in the liver was assessed. However, in areas of sustained blood flow, platelet adhesion was significantly increased in IR livers. T-cell adhesion was significantly increased in IR injured livers, with no increases in T- or B-cell adhesion following ConA injury. In thrombocytopenic mice, a significant reduction in T- and B-cell adhesion was observed in both IR and ConA livers. Blocking CD162 (PSGL-1) on T-cells significantly decreased their recruitment in both injury models. Our data demonstrates adhesion of both T- and B-cells within the hepatic microcirculation in both injury models is platelet dependent. Interestingly, lymphocyte adhesion within healthy liver was not platelet dependent. Collectively, our results suggest platelets play a key role in mediating lymphocyte recruitment to injured liver.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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