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

Complement receptor 3 (CR3), also known as Integrin alpha-M beta-2 (CD11b/CD18) or Mac-1, is a heterodimeric integrin receptor primarily expressed on myeloid cells like neutrophils and macrophages (UniProt P11215). It contains a specialized lectin-like domain located C-terminal to the I-domain on the CD11b subunit, which specifically binds microbial carbohydrates such as beta-glucans (Vetvicka et al., 1996, J. Clin. Invest.). Binding of ligands to this lectin domain induces a conformational change that primes the receptor, allowing it to trigger phagocytosis and degranulation when the I-domain subsequently binds iC3b-opsonized targets (Ross et al., 1999, Immunopharmacology). In oncology, the lectin domain is a therapeutic target for beta-glucan-based agents like Imprime PGG, which aim to enhance the anti-tumor efficacy of monoclonal antibodies by activating complement-dependent cellular cytotoxicity (Bose et al., 2013, J. Immunol.). Beyond cancer, CR3 plays a critical role in inflammatory diseases and leukocyte recruitment, making its modulation a strategy for treating autoimmune disorders and ischemia-reperfusion injury (Hajishengallis et al., 2005, J. Immunol.). The dual-binding nature of CR3—utilizing both the I-domain for protein ligands and the lectin domain for polysaccharides—makes it a unique bridge between the innate and adaptive immune systems.

Other names

Mac-1CD11b/CD18ITGAM/ITGB2Macrophage-1 antigenLectin-like domain of CR3

Agonism of the lectin-like domain primes the receptor for enhanced cytotoxic activity against iC3b-opsonized targets; antagonism or modulation of the I-domain inhibits leukocyte recruitment and inflammatory signaling.