I Thielmann1, D Stegner, P Kraft, I Hagedorn, G Krohne, C Kleinschnitz, G Stoll, B Nieswandt. 1. Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Würzburg, Würzburg Department of Neurology, University of Würzburg, Würzburg Biocenter, University of Würzburg, Würzburg, Germany.
Abstract
BACKGROUND: Platelet activation and aggregation are crucial for primary hemostasis, but can also result in occlusive thrombus formation. Agonist-induced platelet activation involves different signaling pathways leading to the activation of phospholipases, which produce second messengers. The role of phospholipase C (PLC) in platelet activation is well established, but less is known about the relevance of phospholipase D (PLD). OBJECTIVE AND METHODS: The aim of this study was to determine a potential function of PLD2 in platelet physiology. Thus, we investigated the function of PLD2 in platelet signaling and thrombus formation, by generating mice lacking PLD2 or both PLD1 and PLD2. Adhesion, activation and aggregation of PLD-deficient platelets were analyzed in vitro and in vivo. RESULTS: Whereas the absence of PLD2 resulted in reduced PLD activity in platelets, it had no detectable effect on the function of the cells in vitro and in vivo. However, the combined deficiency of both PLD isoforms resulted in defective α-granule release and protection in a model of FeCl3 -induced arteriolar thrombosis, effects that were not observed in mice lacking only one PLD isoform. CONCLUSION: These results reveal redundant roles of PLD1 and PLD2 in platelet α-granule secretion, and indicate that this may be relevant for pathologic thrombus formation.
BACKGROUND: Platelet activation and aggregation are crucial for primary hemostasis, but can also result in occlusive thrombus formation. Agonist-induced platelet activation involves different signaling pathways leading to the activation of phospholipases, which produce second messengers. The role of phospholipase C (PLC) in platelet activation is well established, but less is known about the relevance of phospholipase D (PLD). OBJECTIVE AND METHODS: The aim of this study was to determine a potential function of PLD2 in platelet physiology. Thus, we investigated the function of PLD2 in platelet signaling and thrombus formation, by generating mice lacking PLD2 or both PLD1 and PLD2. Adhesion, activation and aggregation of PLD-deficient platelets were analyzed in vitro and in vivo. RESULTS: Whereas the absence of PLD2 resulted in reduced PLD activity in platelets, it had no detectable effect on the function of the cells in vitro and in vivo. However, the combined deficiency of both PLD isoforms resulted in defective α-granule release and protection in a model of FeCl3 -induced arteriolar thrombosis, effects that were not observed in mice lacking only one PLD isoform. CONCLUSION: These results reveal redundant roles of PLD1 and PLD2 in platelet α-granule secretion, and indicate that this may be relevant for pathologic thrombus formation.
Authors: Maria A Frias; Suman Mukhopadhyay; Elyssa Lehman; Aleksandra Walasek; Matthew Utter; Deepak Menon; David A Foster Journal: J Biol Chem Date: 2019-11-24 Impact factor: 5.157
Authors: Heather M Brechbuhl; Kiran Vinod-Paul; Austin E Gillen; Etana G Kopin; Kari Gibney; Anthony D Elias; Masanori Hayashi; Carol A Sartorius; Peter Kabos Journal: Mol Carcinog Date: 2020-08-21 Impact factor: 4.784
Authors: Raja-Elie E Abdulnour; Judie A Howrylak; Alexander H Tavares; David N Douda; Karen M Henkels; Taylor E Miller; Laura E Fredenburgh; Rebecca M Baron; Julian Gomez-Cambronero; Bruce D Levy Journal: J Leukoc Biol Date: 2018-02-13 Impact factor: 4.962