Platelet secretion is crucial to prevent bleeding in the ischemic brain but not in the inflamed skin or lung in mice
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Platelet secretion is crucial to prevent bleeding in the ischemic brain but not in the inflamed skin or lung in mice. / Deppermann, Carsten; Kraft, Peter; Volz, Julia; Schuhmann, Michael K; Beck, Sarah; Wolf, Karen; Stegner, David; Stoll, Guido; Nieswandt, Bernhard.
in: BLOOD, Jahrgang 129, Nr. 12, 23.03.2017, S. 1702-1706.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Platelet secretion is crucial to prevent bleeding in the ischemic brain but not in the inflamed skin or lung in mice
AU - Deppermann, Carsten
AU - Kraft, Peter
AU - Volz, Julia
AU - Schuhmann, Michael K
AU - Beck, Sarah
AU - Wolf, Karen
AU - Stegner, David
AU - Stoll, Guido
AU - Nieswandt, Bernhard
N1 - © 2017 by The American Society of Hematology.
PY - 2017/3/23
Y1 - 2017/3/23
N2 - Platelets maintain hemostasis after injury, but also during inflammation. Recent studies have shown that platelets prevent inflammatory bleeding through (hem) immunoreceptor tyrosine-based activation motif-dependent mechanisms irrespective of aggregation during skin and lung inflammation. Although the exact mechanisms underlying this process remain unknown, it was speculated that mediators released from platelet granules might be involved. Maintaining cerebral hemostasis during stroke treatment is of high clinical relevance because hemorrhage may aggravate the disease state and increase mortality. Although it was shown that platelets help maintain hemostasis in the ischemic brain, their exact contribution remains ill defined. Here we show that Unc13d -/- /Nbeal2 -/- mice, which lack platelet α- and dense-granule secretion, show no signs of hemorrhage in models of skin or lung inflammation. In stark contrast, lack of platelet granule release resulted in impaired hemostasis in the ischemic brain after transient middle cerebral artery occlusion leading to increased intracranial hemorrhage and mortality. Our results reveal for the first time that platelet granule constituents are essential for maintenance of hemostasis during thrombo-inflammatory brain infarction but not experimental inflammation of the skin or lung, thereby uncovering vascular bed-specific differences in the prevention of inflammatory bleeding.
AB - Platelets maintain hemostasis after injury, but also during inflammation. Recent studies have shown that platelets prevent inflammatory bleeding through (hem) immunoreceptor tyrosine-based activation motif-dependent mechanisms irrespective of aggregation during skin and lung inflammation. Although the exact mechanisms underlying this process remain unknown, it was speculated that mediators released from platelet granules might be involved. Maintaining cerebral hemostasis during stroke treatment is of high clinical relevance because hemorrhage may aggravate the disease state and increase mortality. Although it was shown that platelets help maintain hemostasis in the ischemic brain, their exact contribution remains ill defined. Here we show that Unc13d -/- /Nbeal2 -/- mice, which lack platelet α- and dense-granule secretion, show no signs of hemorrhage in models of skin or lung inflammation. In stark contrast, lack of platelet granule release resulted in impaired hemostasis in the ischemic brain after transient middle cerebral artery occlusion leading to increased intracranial hemorrhage and mortality. Our results reveal for the first time that platelet granule constituents are essential for maintenance of hemostasis during thrombo-inflammatory brain infarction but not experimental inflammation of the skin or lung, thereby uncovering vascular bed-specific differences in the prevention of inflammatory bleeding.
KW - Animals
KW - Blood Platelets/metabolism
KW - Brain Ischemia/blood
KW - Cerebral Hemorrhage/blood
KW - Hemorrhage/pathology
KW - Hemostasis
KW - Infarction, Middle Cerebral Artery
KW - Inflammation/blood
KW - Lung/pathology
KW - Mice
KW - Secretory Vesicles/physiology
KW - Skin/pathology
U2 - 10.1182/blood-2016-12-750711
DO - 10.1182/blood-2016-12-750711
M3 - SCORING: Journal article
C2 - 28077416
VL - 129
SP - 1702
EP - 1706
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 12
ER -