Abstract

Toll-like receptors (TLR) comprise a family of transmembrane proteins characterized by multiple copies of leucine-rich repeats in the extracellular domain and an IL-1 receptor motif in their cytoplasmic domain. The TLR family is a phylogenetically conserved mediator of innate immunity that is essential for microbial recognition and the stimulation of adaptive immune responses. Recently, our laboratory demonstrated that TLR4 expression on platelets was responsible for lipopolysaccharide (LPS)-mediated thrombocytopenia and tumour necrosis factor-α production in vivo (

Aslam et al.
Blood
107
:
637
,
2006
). To understand the mechanism of how platelet TLR4 may mediate RES activation, platelets from wild type (WT) and TLR4 knockout mice were incubated with various concentrations of LPS in vitro, washed extensively and transfused into WT mice. Results suggest that only the WT platelets could significantly stimulate TNF-α production in vivo. In vitro flow cytometric analysis of phagocytosis by the monocytic cell line THP-1 demonstrated that platelet TLR4 could efficiently present LPS to THP-1 cells and stimulated them to engulf the LPS-coated platelets. The phagocytosis of the platelets was correlated to elevated levels of intracellular TNF-α production in the THP-1 cells. These results suggest that platelets, via TLR4 expression, can act as initial sentinels of the innate immune system by presenting bacterial products such as LPS to phagocytes of the RES.

Disclosure: No relevant conflicts of interest to declare.

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