Thrombospondin‐1: a unique marker to identify in vitro platelet activation when monitoring in vivo processes
| Autor: | Alice Assinger, Christine Brostjan, Herwig P. Moll, T. Gruenberger, Sebastian F. Schoppmann, Birgit Gruenberger, Patrick Starlinger, Konrad Hoetzenecker, Michael Gnant, C. Nemeth, Irene Kuehrer |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Gene isoform Time Factors In Vitro Techniques Pharmacology Biology Thrombospondin 1 Platelet degranulation In vivo Neoplasms Humans Protein Isoforms Platelet Platelet activation Aged Wound Healing Temperature Hematology Middle Aged Platelet Activation Recombinant Proteins In vitro Case-Control Studies Immunology Female Wound healing |
| Zdroj: | Journal of Thrombosis and Haemostasis. 8:1809-1819 |
| ISSN: | 1538-7836 |
| DOI: | 10.1111/j.1538-7836.2010.03908.x |
| Popis: | Summary. Background: Measuring platelet activation in patients has become a potent method to investigate pathophysiological processes. However, the commonly applied markers are sensitive to detrimental influences by in vitro platelet activation during blood analysis. Objectives: Protein isoforms of platelet-derived thrombospondin-1 (TSP-1) were investigated for their potential to identify in vitro platelet activation when monitoring in vivo processes. Methods: TSP-1 was determined in plasma, serum or supernatant of purified platelets by ELISA and immunoblotting and was compared with standard markers of platelet activation. A collective of 20 healthy individuals and 30 cancer patients was analyzed. Results: While in vitro platelet degranulation led to a selective increase in the 200-kDa full-length molecule, an in vivo process involving platelet activation such as wound healing resulted in the predominant rise of the 140-kDa TSP-1 protein. The physiological ratio of circulating TSP-1 variants was determined and a cut-off level at 1.0 was defined to identify plasma samples with artificial in vitro platelet activation exceeding the cut-off level. In contrast, cancer patients known to frequently exhibit increased in vivo activation of platelets presented with a significantly decreased ratio of TSP-1 variants as compared with healthy volunteers. Conclusions: In comparison to standard platelet markers, TSP-1 constitutes a sensitive and stable parameter suited to monitor in vitro platelet activation. The analysis of TSP-1 protein isoforms further offers a valuable tool to reliably discriminate between in vitro and in vivo effects, to exclude variability introduced during blood processing and improve clinical monitoring. |
| Databáze: | OpenAIRE |
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