A dichotomy in platelet activation: Evidence of different functional platelet responses to inflammatory versus haemostatic stimuli. Issue 172 (December 2018)

• Record Type: Journal Article
• Authors: Petito, Eleonora; Amison, Richard T.; Piselli, Elisa; Shah, Sajeel A.; Momi, Stefania; Pitchford, Simon C.; Gresele, Paolo; Page, Clive P.
• Is Part Of: Thrombosis research. Issue 172(2018)
• Page Start: 110
• Page End: 118
• Publication Date: 2018-12
• Subjects: 5-HT serotonin -- 5HT-2A serotonin 2A receptor -- 7TM-GPCRs 7-transmembrane G-protein-coupled receptors -- ACD acid citrate dextrose -- ADP adenosine diphosphate -- ALI acute lung injury -- ANOVA analysis of variance -- ARDS acute respiratory distress syndrome -- CCR4 CC chemokine receptor 4 -- Coll collagen -- COPD chronic obstructive pulmonary disease -- CVX convulxin -- CXCR4 CXC chemokine receptor 4 -- CXCR7 CXC chemokine receptor 7 -- DAMPs danger-associated molecular patterns -- EDTA ethylenediaminetetraacetic acid -- Epi epinephrine -- FcεRI high-affinity IgE receptor, or Fc epsilon receptor I -- FITC fluorescein isothiocyanate -- fMLP N-formyl-methionyl-leucyl-phenylalanine -- FPR formyl peptide receptor -- GEFs guanine nucleotide exchange factors -- GPVI glycoprotein VI -- GTP guanosine triphosphate -- H1, H2 histamine receptors -- Hist histamine -- IgE Immunoglobulin E -- IL1-R1 Interleukin 1 receptor, type 1 -- IL-1β interleukin-1β -- ITAM immunoreceptor tyrosine-based activation motif -- LPS lipopolysaccharide -- LTA light transmission aggregometry -- MDC/CCL22 macrophage-derived chemokine -- Na3VO4 sodium orthovanadate -- NaCl sodium chloride -- NaF sodium fluoride -- NSAIDs nonsteroidal anti-inflammatory drugs -- PAF platelet activating factor -- Pam3CSK4 Pam3-Cys-Ser-Lys-Lys-Lys-Lys -- PAR-1 protease activated receptor 1 -- PC5 phycoerythrin cyanin 5 -- PF-4 platelet factor 4 -- PI protease inhibitors -- PLC phospholipase C -- PRP platelet rich plasma -- RANTES regulated on activation, normal T cell expressed and secreted -- SDF-1α/CXCL12 stromal cell-derived factor-1α -- SDS-PAGE sodium dodecyl sulfate polyacrylamide gel electrophoresis -- SEM standard error of the mean -- TLR Toll-like receptor -- TP thromboxane receptor -- TRAP-6 thrombin receptor activating peptide-6 -- Tris-HCl Tris hydrochloride -- TxA2 thromboxane A2 -- U46619 TxA2 analogue -- VWF von-Willebrand factor -- β-TG β-thromboglobulin; Chemotaxis -- Haemostasis -- Inflammation -- Leukocytes -- Platelets -- Thrombosis; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2018.10.019
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Introduction: Platelets participate in inflammatory disorders through a variety of different functional responses, including chemotaxis, platelet-leukocyte complex formation and facilitation of leukocyte recruitment that are thought to be distinct from platelet aggregation. This may account for why classical anti-platelet drugs have failed to ameliorate inflammatory disorders where platelets are 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 platelets preferentially involved either in haemostasis or in inflammation. Materials and methods: Human platelets were 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, platelet migration and platelet protein phosphorylation were assessed. Results: Haemostatic stimuli induced platelet aggregation, whilst inflammatory agonists induced platelet migration. 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 phosphorylation compared with haemostatic stimuli. Conclusions: Stimulation of platelets with inflammatory stimuli triggers the activation of non haemostatic functions different from those induced by haemostatic stimuli, supporting the existence of alternative platelet responses 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. Highlights: Platelet functional responses in haemostasis and inflammation are different. Haemostatic stimuli induce aggregation whereas inflammatory stimuli induce migration, but not aggregation. A different platelet response depending on the activating stimulus exists.