A dichotomy in platelet activation: Evidence of different functional platelet responses to inflammatory versus haemostatic stimuli

Abstract Introduction Plateletsparticipate in inflammatory disordersthrough a variety of different functional responses, including chemotaxis, platelet-leukocyte complex formation and facilitation of leukocyte recruitment that are thought to be distinct from plateletaggregation. This may account for why classical anti- plateletdrugs have failed to ameliorate inflammatory disorderswhere plateletsare known to participate, suggesting that distinct pathways may control inflammatory and haemostatic functions of platelets. In the present study, we have therefore investigated the effect of different stimuli on several different functions of plateletspreferentially involved either in haemostasis or in inflammation. Materials and methods Human plateletswere stimulated with either inflammatory (fMLP, histamine, IL-1β, LPS, MDC/ CCL22, SDF-1α/CXCL12 and 5-HT) or haemostatic (ADP, collagen, convulxin, epinephrine, TRAP-6 and U46619) stimuli. Aggregation, platelet-leukocyte complex formation, plateletmigration and platelet protein phosphorylationwere assessed. Results Haemostatic stimuli induced plateletaggregation, whilst inflammatory agonists induced plateletmigration. The haemostatic stimuli, with the exception of epinephrine, and some of the inflammatory stimuli induced platelet-leukocyte complex formation, even if to a different extent. Furthermore, inflammatory stimuli induced a shorter lasting profile of platelet protein phosphorylationcompared with haemostatic stimuli. Conclusions Stimulation of plateletswith inflammatory stimuli triggers the activation of non haemostatic functions different from those induced by haemostatic stimuli, supporting the existence of alternative plateletresponses depending on the stimulus (haemostatic or inflammatory). A deeper understanding of the biochemical pathways behind these functional differences may lead to the development of novel therapeutic options targeting the inflammatory actions of platelets, without affecting their critical role in haemostasis.