Integrin alpha-M beta-2 – Platelet glycoprotein Ib alpha chain protein–protein interaction (Mac-1 – GPIbα PPI)

The Integrin alpha-M beta-2 (Mac-1) – Platelet glycoprotein Ib alpha chain (GPIbα) protein-protein interaction is a critical molecular bridge between leukocytes and platelets, mediating heterotypic cell adhesion at sites of vascular injury (Wang et al., 2017). Mac-1, a member of the β2-integrin family expressed on myeloid cells, binds to the GPIbα subunit of the platelet GPIb-IX-V complex, facilitating leukocyte recruitment and thrombus stabilization (Simon et al., 2005). This interaction triggers 'outside-in' signaling pathways, such as the downregulation of the transcription factor Foxp1 and the induction of pro-thrombotic factors like tissue factor and neutrophil extracellular traps (NETs) (Wang et al., 2017). Unlike traditional antithrombotic therapies that target platelet aggregation or coagulation factors, disrupting the Mac-1 – GPIbα interaction offers a strategy to inhibit thrombosis and vascular inflammation without significantly impairing hemostasis or increasing bleeding risk (Wang et al., 2017). Consequently, it is a promising therapeutic target for conditions characterized by thromboinflammation, including myocardial infarction, stroke, and restenosis (Simon et al., 2005). Small molecules like glucosamine and specific antibodies like anti-M2 have been identified to selectively disrupt this interaction, demonstrating efficacy in preclinical models (Wang et al., 2017).

Other names

Mac-1 – GPIbα interactionCD11b/CD18 – CD42b interactionIntegrin alpha-M beta-2 – Glycoprotein Ib alpha interactionLeukocyte-platelet adhesion complexMacrophage-1 antigen – Platelet glycoprotein Ib alpha interaction

Selective inhibition of the protein-protein interaction between the Mac-1 I-domain and the GPIbα leucine-rich repeat region to prevent leukocyte-platelet adhesion and subsequent thromboinflammatory signaling.