Complement receptor 3 and Complement receptor 4 (CR3 and CR4)

Complement receptor 3 (CR3) and Complement receptor 4 (CR4) are heterodimeric integrins belonging to the beta-2 family, primarily expressed on the surface of myeloid cells such as neutrophils, monocytes, and macrophages [1][2]. CR3 is composed of the alpha-M (CD11b) and beta-2 (CD18) subunits, while CR4 consists of alpha-X (CD11c) and beta-2 (CD18) subunits [1]. These receptors are vital for the innate immune response, mediating the phagocytosis of iC3b-opsonized pathogens and facilitating leukocyte adhesion to the endothelium through interactions with ligands like ICAM-1 [3][4]. In the context of wild-type induced neutrophils (WT-iNeuts), CR3 and CR4 serve as essential functional markers, and their expression is a hallmark of successful neutrophil maturation from pluripotent stem cells [5]. Dysregulation of these receptors is associated with inflammatory diseases, autoimmune conditions like systemic lupus erythematosus, and Leukocyte Adhesion Deficiency (LAD) [6]. Therapeutic modulation of CR3 and CR4, using small molecules like Leukadherin-1 or monoclonal antibodies, aims to either suppress excessive inflammation or enhance the clearance of pathogens and apoptotic cells [7][8].

Other names

CD11b/CD18Mac-1Integrin alpha-M beta-2CD11c/CD18p150,95Integrin alpha-X beta-2ITGAM/ITGB2ITGAX/ITGB2

Modulation of the integrin alpha-subunit I-domain to alter affinity for ligands such as iC3b and ICAM-1, thereby regulating leukocyte recruitment and phagocytic activity [7][8].