Macrophage-1 antigen – Platelet glycoprotein Ib alpha chain interface (Mac-1–GPIbα interface)

The Mac-1–GPIbα interface is a specialized protein-protein interaction that bridges leukocytes and platelets, serving as a key driver of thromboinflammation. Mac-1 (Integrin alpha-M beta-2 or CD11b/CD18) is a prominent integrin on the surface of neutrophils and monocytes, while Glycoprotein Ib alpha (GPIbα) is the primary ligand-binding subunit of the GPIb-V-IX complex on platelets (Wang et al., 2005, J Exp Med). This interaction is essential for the stable adhesion of leukocytes to the vascular wall and to developing thrombi, particularly under high-shear conditions (Simon et al., 2000, Circulation). In pathological states such as myocardial infarction, stroke, and deep vein thrombosis, the Mac-1–GPIbα interface facilitates excessive leukocyte recruitment, which promotes tissue damage and vascular occlusion (Schulz et al., 2013, Nat Rev Cardiol). Unlike traditional anti-thrombotic agents that target platelet aggregation and carry significant bleeding risks, therapeutic strategies targeting this specific interface aim to decouple inflammation from thrombosis (Zuchtriegel et al., 2016, Nat Commun). Experimental inhibitors, including specific peptides and monoclonal antibodies, have demonstrated the potential to reduce inflammatory injury while preserving primary hemostasis, making this interface a high-value target for cardiovascular drug development.

Other names

CD11b/CD18–GPIbα interactionIntegrin alpha-M beta-2–GPIb alpha interfaceLeukocyte-platelet interfaceMac-1–GPIb alpha complex

Disruption of the physical interaction between the Mac-1 I-domain on leukocytes and the leucine-rich repeat domain of GPIbα on platelets to inhibit thromboinflammatory signaling.