Toll‐like receptor 4 ligand can differentially modulate the release of cytokines by human platelets

Abstract

Summary Blood platelets link the processes of haemostasis and inflammation. This study examined the immunomodulatory factors released by platelets after Toll‐Like Receptor 4 (TLR4) engagement on their surfaces. Monoclonal anti‐human FcγRII Ab (IV.3)‐treated human platelets were cultured with TLR4 ligands in the presence or absence of blocking monoclonal antibody to human TLR4. The release of sCD62p, epidermal growth factor (EGF), transforming growth factor β (TGFβ), interleukin (IL)‐8, platelet activating factor 4 (PAF4), platelet‐derived growth factor, α, β polypeptide (PDGF‐AB), Angiogenin, RANTES (regulated upon activation, normal T‐cell expressed, and presumably secreted) and sCD40L were measured by specific enzyme‐linked immunosorbent assay. TLR4 ligand [Escherichia coli lipopolysaccharide (LPS)] bound platelet TLR4, which differentially modulates the release of cytokines by platelets. It was noted that (i) sCD62p, IL‐8, EGF and TGFβ release were each independent of platelet activation after TLR4 engagement; (ii) RANTES, Angiogenin and PDGF‐AB concentration were weaker in platelet supernatant after TLR4 engagement; (iii) sCD40L and PAF4 are present in large concentration in the releaseate of platelets stimulated by TLR4 ligand. The effects of LPS from E. coli on the modulation of secretory factors were attenuated by preincubation of platelets with an anti‐TLR4 monoclonal antibody, consistent with the immunomodulation being specifically mediated by the TLR4 receptor. We propose that platelets adapt the subsequent responses, with polarized cytokine secretion, after TLR4 involvement.

Platelets can enhance vascular permeability

“…Indeed, the growing appreciation of platelet's capability to make available certain type of granule's mediators under different conditions is in agreement with this hypothesis. 65,66 In conclusion, we revealed an unpredicted role for platelets in vasculature during inflammatory arthritis. Platelet serotonin coordinates the formation of gaps between endothelial cells in the joint microvasculature, of dimensions compatible with those of platelet MPs and immune complexes, and with their extrusion into the synovial space.…”

Platelets: Guardians of Tumor Vasculature

“…Platelets have two different types of granules, dense granules where serotonin is located and alpha granules containing protein components including angiogenic factors, growth factors, and immunomodulatory cytokines. The alpha granules further differ in their composition and can be differentially secreted by platelets depending on stimulus (9,28) as is the case for endothelial storage granules (29). Thus, there could be a very fine regulation of expression of angiogenic, inflammatory, and vascular stability modulators by granular secretion within the tumor.…”

Markers of Platelet Activation Are Increased in Adolescents With Type 2 Diabetes

“…Plasma concentrations of plateletderived activation markers, soluble CD62P (sCD62P), soluble CD40 ligand (sCD40L, a proinflammatory mediator), and platelet factor 4 (PF4, a chemokine stored in platelet a-granules) were measured in triplicate by ELISA (R&D Systems Europe Ltd., Lille, France; or AbCys, Paris, France) (8). Coefficients of variation for all assays were #10%.…”