Lilleana Rogers

Primary Author: Lilleana Rogers, MS2

Author: Dr. Aaron Petry, Kimberly Quisser, Nansy Albtoush, Rebecca Mellema, Lydia Smith, Julie Will, Dr. John F. Valentine

Acknowledgements: University of Utah Molecular Medicine Program, National Institute of Diabetes and Digestive and Kidney DiseasesPlatelet Reactivity In Inflammatory Bowel DiseaseIndividuals with Inflammatory Bowel Disease (IBD) have larger sized and elevated numbers of platelets and rates of platelet activation, thus increasing patient risk for microvascular thrombosis and thromboembolisms. Platelets have Toll-Like Receptors (TLRs), including TLR4 and TLR5 that recognize bacterial lipopolysaccharides (LPS) and flagellin (FLA) respectively. To bind to TLR4, smooth LPS (LPSs) requires the co-receptor CD14, a monocyte derived marker that is absent from healthy platelets but can be scavenged from serum. The binding of LPS and FLA leads to degranulation, aggregation and further platelet activation that can potentiate clotting and inflammation. This study is directed to investigate the role of platelet reactivity when exposed to TLR agonists in patients with IBD. Washed platelets from healthy donors (HD) and IBD patients were incubated with various LPSs and FLA concentrations before being mixed with thrombin, a known platelet activator, and fluorescent antibodies. The platelets were then fixed and analyzed with Flow Cytometry. Antibodies against PAC-1, a marker for active glycoprotein IIb/IIIa, and P-Selectin, a marker for alpha-degranulation, were used to measure activation levels. Platelets were also incubated with various receptor antibodies. Key results include that though concentrations of TLR4 and TLR5 are similar between HD and IBD platelets, IBD platelets had significantly increased concentrations of CD14. HD platelets had greater levels of activation in regards to PAC-1 levels when exposed to thrombin alone and LPS or FLA alone, suggesting IBD platelet exhaustion or transcriptional changes. However, IBD platelets showed a greater increase of activation following incubation with LPS and thrombin. This data indicates that the increased concentration of CD14 on IBD platelets allows LPS to further enhance activation of platelets when compared to that of HDs. This difference could play a role in the pathogenesis and perpetuation of disease in IBD and be a target for future therapies.