Evidence of Toll‐like receptor molecules on human platelets

Abstract

Summary Platelets are primarily involved in thrombosis and haemostasis, and they have recently been shown to have a role in innate immunity and in inflammation. We have determined the markers of innate immunity that are expressed by platelets, specifically the Toll-like receptors (TLR), originating from mixes of platelet concentrates (MPC, n = 5) between day zero and day five after blood collection. The surface membrane and intracellular expression of TLR were measured, both after and without permeabilization, using flow cytometry. We observed weak expression of TLR2, TLR4 and TLR9 on the surface of CD41 + platelets. The expression levels of TLR4 were high (59 ± 2.2%). Moreover, there was a significant expression of TLR2 (47.5 ± 4.8%), TLR4 (78.8 ± 1.3%) and TLR9 (34.2 ± 7.5%) in the cytoplasm of CD41 + platelets. The expression of the three receptors did not change significantly during the course of the 5 day observation period. The percentage of TLR expression is significantly modulated between activated versus non-activated platelets, both after and without permeabilization ( P < 0.01). Study of the expression of TLR could increase our knowledge of the level of platelet participation during an immune reaction and inflammation. In the same way as the platelet ligand/receptor pair CD40L/CD40 is, the TLR are expressed by platelets, and could serve as a link between innate and adaptive immunity.

Platelets regulate leucocyte responses to Toll‐like receptor stimulation

“…Platelets are known to express various TLRs,5 and TLR stimulation can mediate a number of thrombotic7, 8, 21 and inflammatory processes 9, 10. Platelets and leucocytes aggregate in response to TLR stimulation,9, 12 and platelets contribute to vascular inflammation via this interaction with leucocytes.…”

“…In infection‐related vascular injury, platelets are important effectors of antimicrobial host defence1 and platelets also enhance leucocyte effector functions in a number of inflammatory pathologies which are characterised by sterile vascular injury 2, 3, 4. Platelets express a range of Toll‐like receptors (TLRs),5, 6 which are responsible for mediating early immune responses to both infection and sterile injury. Activating platelet‐TLRs causes platelet activation and aggregation7, 8 alongside a number of pro‐inflammatory, antimicrobial responses 9, 10, 11.…”

Receptors involved in cell activation by antiphospholipid antibodies

“…Increased expression of TLR2 by EC in response to inflammatory mediators such as TNF, LPS, IL-1β, IFNγ and histamine in vivo and in vitro [49][50][51][52], however, provides a mechanism allowing EC to respond to TLR2 ligands under inflammatory conditions. TLR2 and TLR4 are both expressed on platelets [53] and on monocytes [54]. Sorice et al [55] have identified that TLR4, β2GP1 and annexin A2 form an activation cluster in plasma membrane microdomains of human monocytes after LPS or aPLA ligation.…”

Plaquetas: Papéis tradicionais e não tradicionais na hemostasia, na inflamação e no câncer

“…Assim, nos anos 2004 e 2005, Shiraki 33 , Cognasse 34 et al descobriram receptores funcionais Toll-like em ratos e humanos, receptores esses que reconhecem lipopolissacarídeos bacterianos e outros produtos microbianos. A expressão de receptores Toll-like representa uma nova faceta no repertório de interação da plaqueta em resposta à presença de microorganismos e seus sinais moleculares, contribuindo assim para a efetiva função antimicrobiana 1 .…”

“…A expressão de receptores Toll-like representa uma nova faceta no repertório de interação da plaqueta em resposta à presença de microorganismos e seus sinais moleculares, contribuindo assim para a efetiva função antimicrobiana 1 . Além disso, os receptores Toll-like modulam a sinalização inflamatória e respostas trombóticas na sepse e em outras condições patológicas, como o câncer 1,34 . Outros sistemas de transdução de sinais em plaquetas são os ativados por trombina e/ou PAF (platelet activating factor), que também ligam hemostasia e inflamação sob condições fisio-patológicas 16 .…”