Macrophage-1 antigen – Glycoprotein Ib alpha interface (Mac-1 – GPIbα interface)

The Mac-1 – GPIbα interface is a critical protein-protein interaction (PPI) that mediates the physical adhesion between leukocytes and platelets, serving as a primary bridge between the immune and thrombotic systems (Wang et al., 2005, J. Exp. Med.). Mac-1 (Integrin αMβ2 or CD11b/CD18) is expressed on the surface of neutrophils and monocytes, while Glycoprotein Ib alpha (GPIbα) is the major ligand-binding subunit of the GPIb-IX-V complex on platelets (Simon et al., 2000, Circulation). This interaction is primarily facilitated by the binding of the Mac-1 I-domain to the leucine-rich repeat (LRR) region of GPIbα, a process essential for leukocyte recruitment to thrombi and the vascular wall during inflammatory responses. Pathologically, this interface is a key driver of thromboinflammation, contributing to tissue damage in conditions such as myocardial infarction, stroke, and atherosclerosis (Eberhardt & Simon, 2015, Frontiers in Physiology). Therapeutic strategies targeting this interface aim to decouple inflammation from thrombosis, potentially offering a way to reduce inflammatory injury without the high bleeding risks associated with traditional anti-platelet or anticoagulant therapies. Experimental inhibitors, including viral-derived proteins like M-T7 and specific inhibitory peptides, have demonstrated efficacy in reducing leukocyte infiltration and vascular damage in preclinical models (Dai et al., 2009, J. Biol. Chem.).

Other names

Integrin alpha-M beta-2 – Glycoprotein Ib alpha interfaceCD11b/CD18 – CD42b interfaceMac-1 – GPIb alpha interactionLeukocyte-platelet interface

Inhibition of the physical protein-protein interaction between the Mac-1 integrin on leukocytes and the GPIbα receptor on platelets to prevent leukocyte-platelet aggregate formation and subsequent inflammatory signaling.