P2X1 ion channel deficiency causes massive bleeding in inflamed intestine and increases thrombosis.
anemia
blood platelets
inflammation
intestine
neutrophils
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
19
03
2019
revised:
09
08
2019
accepted:
21
08
2019
pubmed:
27
8
2019
medline:
15
5
2021
entrez:
27
8
2019
Statut:
ppublish
Résumé
Intestinal inflammation is associated with bleeding and thrombosis, two processes that may involve both platelets and neutrophils. However, the mechanisms and the respective contribution of these cells to intestinal bleeding and extra-intestinal thrombosis remain largely unknown. Our study aimed at investigating the mechanisms underlying the maintenance of vascular integrity and thrombosis in intestinal inflammation. We used a mouse model of acute colitis induced by oral administration of dextran sodium sulfate (DSS) for 7 days. Bleeding was assessed after depletion of platelets, neutrophils, or glycoprotein VI (GPVI); treatment with aspirin or clopidogrel; or in P2X1-deficient mice. Extra-intestinal thrombosis was analyzed using a laser-induced injury model of thrombosis in cremaster muscle arterioles. Platelet depletion or P2X1 deficiency led to macrocytic regenerative anemia due to intestinal hemorrhage. In contrast, GPVI, P2Y12, and thromboxane A Platelets and P2X1 ion channels are mandatory to preserve vascular integrity in inflamed intestine. Upon P2X1 deficiency, neutrophils contribute to bleeding and they may also be responsible for enhanced thrombosis.
Sections du résumé
BACKGROUND
Intestinal inflammation is associated with bleeding and thrombosis, two processes that may involve both platelets and neutrophils. However, the mechanisms and the respective contribution of these cells to intestinal bleeding and extra-intestinal thrombosis remain largely unknown.
OBJECTIVE
Our study aimed at investigating the mechanisms underlying the maintenance of vascular integrity and thrombosis in intestinal inflammation.
METHODS
We used a mouse model of acute colitis induced by oral administration of dextran sodium sulfate (DSS) for 7 days. Bleeding was assessed after depletion of platelets, neutrophils, or glycoprotein VI (GPVI); treatment with aspirin or clopidogrel; or in P2X1-deficient mice. Extra-intestinal thrombosis was analyzed using a laser-induced injury model of thrombosis in cremaster muscle arterioles.
RESULTS
Platelet depletion or P2X1 deficiency led to macrocytic regenerative anemia due to intestinal hemorrhage. In contrast, GPVI, P2Y12, and thromboxane A
CONCLUSIONS
Platelets and P2X1 ion channels are mandatory to preserve vascular integrity in inflamed intestine. Upon P2X1 deficiency, neutrophils contribute to bleeding and they may also be responsible for enhanced thrombosis.
Identifiants
pubmed: 31448510
doi: 10.1111/jth.14620
pii: S1538-7836(22)01560-4
doi:
Substances chimiques
Receptors, Purinergic P2X1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
44-56Informations de copyright
© 2019 International Society on Thrombosis and Haemostasis.
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