Abstract 12482: Innate Immunity via Toll-Like Receptor 4 is Associated With Platelet Activation and Inflammatory Response in Patients With Acute Coronary Syndrome.
Background Infections have been implicated in the etiology of atherosclerosis and its complications. Recent studies have shown acute infections are associated with the risk of vascular thrombotic events, such as acute coronary syndrome (ACS). The innate immune system constitutes the first line of host defense against invasion by microorganisms mediated by the family of Toll-like receptors (TLRs). Although platelets play a crucial role in ACS and accumulating evidence demonstrates role of TLR4 in inflammation and innate immunity, little is known about the expression and functionality of platelet TLR4 in the settings of ACS.
Methods and Results Platelets from ACS patients (platelets A) and healthy controls (platelets C) were incubated with lipopolysaccharide (LPS), natural TLR4 ligand. Platelets A shows significant secretion of α-granules as indicated surface P-selectin expression assessed by flow cytometric analysis and enhances aggregation induced by low concentrations of agonists by LPS whereas platelets C does not. The release of RANTES (regulated upon activation, normal T-cell expressed and secreted) and solubleCD40 ligand (sCD40L) are also measured. RANTES and sCD40L are significantly increased in the releaseate stimulated by LPS in platelets A. The effects of LPS on the activation and modulation of secretory factors are attenuated by preincubation of platelets A with a TLR4 neutralizing antibody. And then, whole blood from healthy controls is incubated with LPS. Circulating platelet-neutrophil aggregation is considered a sensitive marker of the interactions that exist between inflammation and thrombosis in specific clinical settings such as ACS. LPS significantly increases platelet-leucocytes aggregation as observed non-stimulated peripheral blood from ACS patients. The effect of LPS on platelet -neutrophil aggregation was almost abolished by a TLR4 neutralizing antibody.
Conclusion LPS increases platelet activation and inflammatory response through TLR 4 in patients with ACS. TLR 4 allows platelets to recognize infectious structures such as LPS and regulate platelet immunity and function in ACS. And therefore, increased platelet reactivity in ACS may also be reflected the TLR4 activation on the other blood cells.
- © 2010 by American Heart Association, Inc.