Integrin alpha-M beta-2 (Mac-1) (Mac-1)

Integrin alpha-M beta-2, commonly known as Mac-1 or CD11b/CD18, is a heterodimeric transmembrane receptor primarily expressed on the surface of myeloid cells, including macrophages, neutrophils, and natural killer cells (UniProt P11215). It serves as a critical mediator of macrophage adherence to the vascular endothelium and extracellular matrix components like fibrinogen and ICAM-1, a process that is essential for leukocyte extravasation and migration to sites of inflammation (PubMed 10523601). Beyond its adhesive properties, Mac-1 functions as Complement Receptor 3 (CR3), which is vital for the phagocytosis of iC3b-opsonized pathogens and the clearance of apoptotic cells (NCBI Gene ID 3684). In various pathological conditions, such as chronic inflammation, autoimmune diseases, and ischemia-reperfusion injury, dysregulated Mac-1 activity leads to excessive tissue infiltration and subsequent damage (PubMed 25661151). Consequently, Mac-1 is a significant therapeutic target; current drug development efforts focus on small-molecule modulators like GB-1275 and Leukadherin-1 that can either inhibit or allosterically tune its ligand-binding affinity to treat inflammatory disorders and certain cancers (PubMed 22307132). However, therapeutic targeting of this receptor must be carefully managed to avoid compromising the host's innate immune defense against bacterial infections (PubMed 17174134).

Other names

CD11b/CD18Complement receptor 3CR3ITGAM/ITGB2Surface antigen alpha-M beta-2Macrophage antigen 1

Allosteric modulation of the CD11b (ITGAM) subunit to stabilize specific conformational states (active or inactive), or competitive antagonism of the I-domain to block interaction with ligands such as ICAM-1, fibrinogen, and iC3b.