Abstract Number: PB1837
Meeting: ISTH 2020 Congress
Background: Platelets ensure the arrest of bleeding under inflammatory conditions through a mechanism relying primarily on GPVI and to a lesser extent on CLEC-2. However, this role of platelets appears independent of the receptors classically involved in the arrest of bleeding i.e. the GPIb-V-IX complex and integrin αIIbβ3 in the reverse passive Arthus (rpA) model. This questions which platelet receptors support stable platelet adhesion at inflammation site, a role played notably by integrins during a trauma.
Aims: To evaluate the role of platelet β1 and β3 integrins in the arrest of bleeding under inflammatory conditions.
Methods: We used an rpA model based on anti-bovine serum albumin (BSA) antibody intradermal injection and BSA intravenous injection to induce cutaneous inflammation. The intranasal lipopolysaccharide and transient middle cerebral artery models were used to induce lung and cerebral inflammation, respectively.
Results: Contrary to mice totally deficient for β3 integrins, those deficient for β3 integrins in the platelet lineage (PF4Cre-β3-/-) presented localized petechial bleedings in the cutaneous rpA model, which was confirmed using αIIb-deficient mice. These results identify a role for platelet αIIbβ3 integrin in inflammatory bleeding. Mice deficient for platelet β1 integrins did not present bleeding in this model, however, mice deficient for both platelet β1 and β3 integrins (PF4Cre-β1-/-/β3-/-) presented more severe cutaneous bleeding compared to PF4Cre-β3-/- indicating a secondary role for platelet β1 integrins and a cooperation between both integrin families in the arrest of cutaneous bleeding under inflammatory conditions. Similar results were obtained under cerebral inflammatory conditions since PF4Cre-β1-/-/β3-/- mice developed cerebral bleeding. On the contrary, platelet integrins do not appear to play a major role in the arrest of pulmonary bleeding under inflammatory conditions.
Conclusions: This study identifies a cooperation between platelet β1 and β3 integrins in the arrest of cutaneous and cerebral bleeding under inflammatory conditions.
To cite this abstract in AMA style:Janus-Bell E, Receveur N, Mouriaux C, Hechler B, Reiser J, Gachet C, Ho-Tin-Noé B, Mangin P. Platelet β1 and β3 Integrins Cooperate to Stop Cutaneous and Cerebral Bleeding under Inflammatory Conditions in Mice [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/platelet-%ce%b21-and-%ce%b23-integrins-cooperate-to-stop-cutaneous-and-cerebral-bleeding-under-inflammatory-conditions-in-mice/. Accessed January 26, 2022.
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