Activated Platelets Upregulate b2 Integrin Mac-1 (CD11b/CD18) on Dendritic Cells, Which Mediates Heterotypic Cell-Cell Interaction

Recent evidence suggests interaction of platelets with dendritic cells (DCs), while the molecular mechanisms mediating this heterotypic cell cross-talk are largely unknown. We evaluated the role of integrin Mac-1 (aMb2, CD11b/CD18) on DCs as a counterreceptor for platelet glycoprotein (GP) Iba. In a dynamic coincubation model, we observed interaction of human platelets with monocyte-derived DCs, but also that platelet activation induced a sharp increase in heterotypic cell binding. Inhibition of CD11b or GPIba led to significant reduction of DC adhesion to platelets in vitro independent of GPIIbIIIa, which we confirmed using platelets from Glanzmann thrombasthenia patients and transgenic mouse lines on C57BL/6 background (GPIba-/-, IL4RGPIba-tg, and muMac1 mice). In vivo, inhibition or genetic deletion of CD11b and GPIba induced a significant reduction of platelet-mediated DC adhesion to the injured arterial wall. Interestingly, only intravascular antiCD11b inhibited DC recruitment, suggesting a dynamic DC -platelet interaction. Indeed, we could show that activated platelets induced CD11b upregulation on Mg2+-preactivated DCs, which was related to protein kinase B (Akt) and dependent on P-selectin and P-selectin glycoprotein ligand 1. Importantly, specific pharmacological targeting of the GPIba-Mac-1 interaction site blocked DC -platelet interaction in vitro and in vivo. These results demonstrate that cross-talk of platelets with DCs is mediated by GPIba and Mac-1, which is upregulated on DCs by activated platelets in a P-selectin glycoprotein ligand 1 -dependent manner. The Journal of Immunology, 2022, 208: 1729-1741.

Automated summary

Recent evidence supports the interaction between platelets and dendritic cells (DCs), but the molecular mechanisms underlying this heterotypic cell cross-talk remain largely unknown. In this study, the researchers found that activated platelets can enhance the binding between human monocyte-derived DCs and platelets in a dynamic incubation model. Inhibition of CD11b and GPIba significantly reduced the adhesion between DCs and platelets in vitro, and the same inhibition also decreased platelet-mediated DC adhesion to the injured arterial wall in vivo.