Toll-like Receptor 4 Ligand Can Differentially Modulate The Release Of Cytokines By Human Platelets

ObjectiveThis study examined the immune activation and the immunomodulatory factors released by platelets with the stimulation of Escherichia coli lipopolysaccharide(LPS) after Toll-Like Receptor 4(TLR4) engagement on their surface,which lead to the activation of platelet and the difference of the release of sytokines.This study shows that the plates are involved in the course of inflammation and Toll-like receptor 4 ligand can differentially modulate the release of cytokines by human plateletsMethodsPlatelet-rich plasma(PRP) were got from blood of 15 healthy person.Platelets were incubated with the anti-human FcγRⅡMonoclonal anti-body to saturate the free FcγRⅡand block FcγRⅡengagement.The PRP were grouped under many parts:1.Stimulating the PRP with LPS which have different concentration(0μg/ml,1μg/ml,3μg/ml and 5μg/ml).Platelet surface expression of TLR4 was determined by flow cytometric analysis.2.The platelet were stimulated with TLR4 ligand LPS,in the presence or absence of a blocking anti-human TLR4 MoAb.And the release of IL-8,β-TG,TNF-αand sCD40L were measured by specific enzyme-linked immunosorbent assay.Results1.IL-8 release was independent of platelet activation after TLR4 engagement(P=0.657);sCD40L,β-TG,TNF-αwere present in large concentration in the releaseate of platelet stimulated by TLR4 ligand(P＜0.01 ).2.Platelet surface expression of TLR4 were decreased after the engagement of LPS,and it was independent to the LPS with different concentration(P＞0.05).3.The effects of LPS from E.coli on the modulation of secretory factors were attenuated by preincubation of platelets an anti-TLR4 Monoclonal antibody.ConclusionWe propose that platelets adapt the subsequent responses with polarized cytokine secretion,after TLR4 involvement.TLR4 ligand bound platelet TLR4, which differentially modulates the release of cytokines by platelets.