Cooperation of platelet beta1 and beta3 integrins in the arrest of inflammatory bleeding in mice

Objective The main function of platelet is to arrest bleeding at sites of injury. They also ensure the arrest of bleeding under inflammatory conditions through a mechanism proposed to rely on ITAM receptors, with GPVI playing a major role and CLEC-2 a secondary role. However, this role of platelets appears independent of the receptors classically involved in the arrest of bleeding, the GPIb-IX complex and integrin alphaIIbbeta3 in the cutaneous reverse passive Arthus (rpA) model. This raises the question of which platelet receptors support stable platelet adhesion at inflammation site, a role played notably by integrins during a trauma. The aim of this study was to evaluate the role of platelet beta1 and beta3 integrins in the arrest of bleeding under inflammatory conditions.

Material and 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 beta3 integrins, those deficient for beta3 integrins in the platelet lineage (PF4Cre-beta3-/-) and those deficient for alphaIIb presented localized petechial bleedings in the cutaneous rpA model. These results point to a central role of platelet alphaIIbbeta3 integrin in the arrest of inflammatory bleeding. Mice deficient for platelet beta1 integrins did not present bleeding in this model while mice deficient for both platelet beta1 and beta3 integrins (PF4Cre-beta1-/-/beta3-/-) developed more severe cutaneous bleeding than PF4Cre-beta3-/-, implying a cooperation between both integrin families in the arrest of bleeding under inflammatory conditions in the skin. Similar results were obtained under cerebral inflammatory conditions since PF4Cre-beta1-/-/beta3-/- mice developed cerebral bleeding. Platelet beta3 integrins were also playing a role in the arrest of pulmonary bleeding under inflammatory conditions after lipopolysaccharide challenge.

Conclusion Altogether, these results identify a role of platelet beta1 and beta3 integrins in the arrest of bleeding under inflammatory conditions in several organs.

Publication History

Article published online:
18 June 2021