Platelet activation parameters and platelet-leucocyte-conjugate formation in glioblastoma multiforme patients
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Platelet activation parameters and platelet-leucocyte-conjugate formation in glioblastoma multiforme patients. / Marx, Sascha; Splittstöhser, Maximilian; Kinnen, Frederik; Moritz, Eileen; Joseph, Christy; Paul, Sebastian; Paland, Heiko; Seifert, Carolin; Marx, Madlen; Böhm, Andreas; Schwedhelm, Edzard; Holzer, Kerstin; Singer, Stephan; Ritter, Christoph A; Bien-Möller, Sandra; Schroeder, Henry W S; Rauch, Bernhard H.
in: ONCOTARGET, Jahrgang 9, Nr. 40, 25.05.2018, S. 25860-25876.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Platelet activation parameters and platelet-leucocyte-conjugate formation in glioblastoma multiforme patients
AU - Marx, Sascha
AU - Splittstöhser, Maximilian
AU - Kinnen, Frederik
AU - Moritz, Eileen
AU - Joseph, Christy
AU - Paul, Sebastian
AU - Paland, Heiko
AU - Seifert, Carolin
AU - Marx, Madlen
AU - Böhm, Andreas
AU - Schwedhelm, Edzard
AU - Holzer, Kerstin
AU - Singer, Stephan
AU - Ritter, Christoph A
AU - Bien-Möller, Sandra
AU - Schroeder, Henry W S
AU - Rauch, Bernhard H
PY - 2018/5/25
Y1 - 2018/5/25
N2 - Patients with glioblastoma multiforme (GBM) suffer from an increased incidence of vascular thrombotic events. However, key influencing factors of the primary hemostasis have not been characterized in GBM patients to date. Thus, the present study determines the activation level of circulating platelets in GBM patients, in-vitro reactivity to agonist-induced platelet stimulation and the formation of circulating platelet-leucocyte conjugates as well as the plasma levels of the proinflammatory lipid mediator sphingosine-1-phosphate (S1P). The endogenous thrombin potential (ETP) was determined as global marker for hemostasis. The 21 GBM patients and 21 gender and age matched healthy individuals enrolled in this study did not differ in mean total platelet count. Basal surface expression of platelet CD63 determined by flow cytometry was significantly increased in GBM patients compared to controls as was observed for the concentration of soluble P-selectin in the plasma of GBM patients. While the ETP was not affected, the immunomodulatory lipid S1P was significantly decreased in peripheral blood in GBM. Interestingly, monocyte expression of PSGL-1 (CD162) was decreased in GBM patient blood, possibly explaining the rather decreased formation of platelet-monocyte conjugates. Our study reveals an increased CD63 expression and P-selectin expression/ secretion of circulating platelets in GBM patients. In parallel a down-modulated PSGL-1 expression in circulating monocytes and a trend towards a decreased formation of heterotypic platelet-monocyte conjugates in GBM patients was seen. Whether this and the observed decreased plasma level of the immunomodulatory S1P reflects a systemic anti-inflammatory status needs to be addressed in future studies.
AB - Patients with glioblastoma multiforme (GBM) suffer from an increased incidence of vascular thrombotic events. However, key influencing factors of the primary hemostasis have not been characterized in GBM patients to date. Thus, the present study determines the activation level of circulating platelets in GBM patients, in-vitro reactivity to agonist-induced platelet stimulation and the formation of circulating platelet-leucocyte conjugates as well as the plasma levels of the proinflammatory lipid mediator sphingosine-1-phosphate (S1P). The endogenous thrombin potential (ETP) was determined as global marker for hemostasis. The 21 GBM patients and 21 gender and age matched healthy individuals enrolled in this study did not differ in mean total platelet count. Basal surface expression of platelet CD63 determined by flow cytometry was significantly increased in GBM patients compared to controls as was observed for the concentration of soluble P-selectin in the plasma of GBM patients. While the ETP was not affected, the immunomodulatory lipid S1P was significantly decreased in peripheral blood in GBM. Interestingly, monocyte expression of PSGL-1 (CD162) was decreased in GBM patient blood, possibly explaining the rather decreased formation of platelet-monocyte conjugates. Our study reveals an increased CD63 expression and P-selectin expression/ secretion of circulating platelets in GBM patients. In parallel a down-modulated PSGL-1 expression in circulating monocytes and a trend towards a decreased formation of heterotypic platelet-monocyte conjugates in GBM patients was seen. Whether this and the observed decreased plasma level of the immunomodulatory S1P reflects a systemic anti-inflammatory status needs to be addressed in future studies.
KW - Journal Article
U2 - 10.18632/oncotarget.25395
DO - 10.18632/oncotarget.25395
M3 - SCORING: Journal article
C2 - 29899827
VL - 9
SP - 25860
EP - 25876
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 40
ER -