Complement Receptor 3 (CD11b+CD18)

CR3 (complement receptor 3) is a heterodimeric protein consisting of α (CD11b) and β (CD18) transmembrane glycoproteins. CD11b is unique for CR3, while CD18 is shared by members of the β2 integrin family including LFA1, CR4, and αdβ2. CR3 is found on monocytes, macrophages, dendritic cells, neutrophils, eosinophils, NK cells, and on some T and B cells. It plays a key role in a variety of biological processes including leucocyte adhesion, activation, recruitment, host defense, phagocytosis, and immune tolerance functions through interacting with numerous ligands such as iC3b, fibrinogen, ICAM-1, ICAM-2, zymosan, factor X, haptoglobin, LPS, and oligodeoxynucleotides. For example, the binding of (1,3)-β-glucan to the lectin domain of CR3 initiates leukocytes for CR3-dependent cytotoxicity of iC3b-bound target cells. Also, CR3 is involved in FcγR-mediated phagocytic cup formation and closure.

Recent studies have reported CR3 is involved in the pathological process of Alzheimer’s disease (AD). The microglial CR3 may play a role in the regulation of soluble β-amyloid (Aβ) clearance independent of phagocytosis. Knockout of CR3 in human amyloid precursor protein-transgenic mice results in a decreased Aβ accumulation. Besides, CR3 was also reported to be involved in the regulation of NADPH oxidase activation and dopaminergic neurodegeneration via an Src-Erk-dependent pathway in a two pesticide-induced Parkinson's disease model. CR3 provides a novel insight into the immune pathogenesis of neurodegenerative diseases.

Fig.1 Schematic diagram showing potential mechanisms for complement receptor 3 (CR3)-dependent microglial phagocytosis of neurons, dendrites, and synapses. (Cañadell, 2020)

Reference

1. Cañadell, M.P.; et al. Sialylation and galectin-3 in microglia-mediated neuroinflammation and Neurodegeneration. Frontiers in Cellular Neuroscience. 2020.