Complement receptor 3 (Integrin alpha-M beta-2) (CR3)

Complement receptor 3 (CR3), also known as Mac-1 or integrin alpha-M beta-2, is a heterodimeric cell surface receptor composed of CD11b (ITGAM) and CD18 (ITGB2) subunits, primarily expressed on myeloid cells such as macrophages, neutrophils, and monocytes (UniProt: P11215). Its primary biological role is the recognition and binding of the complement fragment iC3b, which triggers the phagocytosis of opsonized pathogens and cellular debris, thereby serving as a critical component of the innate immune system (PubMed: 15507525). Additionally, CR3 facilitates leukocyte recruitment and transendothelial migration by interacting with ligands like ICAM-1 and fibrinogen (PubMed: 10603370). In the context of oncology, CR3 is a key marker and functional regulator of myeloid-derived suppressor cells (MDSCs), which contribute to an immunosuppressive environment that allows tumors to evade the immune system (PubMed: 31819004). Therapeutic development has focused on small molecule agonists, such as GB1275, which allosterically modulate the receptor to promote an active conformation; this paradoxically reduces the infiltration of suppressive myeloid cells into tumors and can reprogram them toward a pro-inflammatory phenotype (PubMed: 31819004). Genetic variations in the ITGAM subunit are also strongly associated with susceptibility to systemic lupus erythematosus (SLE), highlighting its importance in autoimmune regulation (PubMed: 18204100).

Other names

Mac-1CD11b/CD18Integrin alpha-M beta-2ITGAM/ITGB2Mo1 antigenOKM1Macrophage-1 antigen

Allosteric modulation of the CD11b subunit to stabilize the active conformation of the CR3 complex, which increases cell adhesion and inhibits the migration of immunosuppressive myeloid cells into the tumor microenvironment (PubMed: 31819004).