Integrin alpha-M beta-2 (CR3) (CR3)

Complement receptor 3 (CR3), also known as Mac-1 or integrin alpha-M beta-2, is a heterodimeric transmembrane glycoprotein primarily expressed on the surface of myeloid cells such as neutrophils, macrophages, and natural killer cells (UniProt P11215, P05107). It consists of the alpha-M subunit (CD11b) and the beta-2 subunit (CD18) and is essential for the innate immune response by mediating the phagocytosis of complement-opsonized (iC3b) pathogens (PubMed: 29038208). CR3 also facilitates leukocyte adhesion to the vascular endothelium by binding to ligands such as Intercellular Adhesion Molecule-1 (ICAM-1), which is a critical step in the extravasation of cells into inflamed tissues. In the context of disease, genetic deficiencies in the CD18 subunit lead to Leukocyte Adhesion Deficiency type 1 (LAD-1), characterized by recurrent bacterial infections (StatPearls: NBK539818). Conversely, overactivation or dysregulation of CR3 is implicated in chronic inflammatory conditions and autoimmune diseases like systemic lupus erythematosus. In oncology, CR3 is being explored as a target to modulate the immunosuppressive activity of myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment. Therapeutic approaches include small molecule agonists that stabilize the receptor's active state to limit pathological migration and monoclonal antibodies designed to block ligand binding and reduce tissue infiltration.

Other names

Mac-1CD11b/CD18Integrin alpha-M beta-2ITGAM/ITGB2Macrophage-1 antigenMO1Complement receptor type 3

CR3-targeted therapies primarily utilize two mechanisms: agonism and antagonism. Agonists, such as Leukadherin-1, stabilize the high-affinity active conformation of the CD11b/CD18 heterodimer, which promotes firm cell adhesion to the endothelium and paradoxically inhibits the directed migration (chemotaxis) of neutrophils and macrophages into tissues (PubMed: 22307132). Antagonists, including various monoclonal antibodies and peptides like M7, block the interaction between CR3 and its ligands (e.g., iC3b, ICAM-1, fibrinogen), thereby preventing opsonophagocytosis and leukocyte recruitment to sites of inflammation (PubMed: 29038208).