Platelet activation responses in vitro to human mast cell activation
Mast cells are thought to play an important role in atherogenesis and plaque rupture, but their role in the subsequent platelet activation and thrombus formation is unclear. Tryptase positive cells (KU812 (T+)) were established from the KU812 cell line as an in vitro model of human mast cells and used to study the effect of mast cell activation on human platelets. Overnight incubation of KU812T+ with IgE and subsequent challenge with anti-IgE caused the release of heparinoid substances which inhibited 1 micro g/ml collagen-induced platelet aggregation. KU812T+ challenged with compound 48/80 produced a releasate that had no apparent heparinoid content but caused full platelet aggregation. These findings showed that, although activation of KU812T+ via Fc epsilon R1 partially abrogated collagen-induced platelet aggregation, activation of the C5a receptor signalling pathway, by compound 48/80, caused the release of potent platelet-activating substances. This cell culture model offers a unique insight into the role of platelet-mast cell interactions in arterial thrombogenesis.