Human Integrin  beta2/CD18 Antibody

Integrin alphaX beta2, also called CD11c/CD18, p150/95 or complement receptor type 4 (CR4), is one of four beta2 integrins. The non-covalent heterodimer of 150 kDa alphaX/CD11c and 95 kDa beta2/CD18 integrin subunits is expressed on macrophages, dendritic cells and hairy cell leukemias, with lower amounts on other myeloid cells and activated B, NK and some cytotoxic T cells (1‑7). Like other integrins, alphaX beta2 has multiple activation states (3). In the presence of divalent cations and "inside-out" signaling, alphaX beta2 is fully active and extended. The alphaX vWFA or I-domain, which contains the adhesion sites, forms the N-terminal head region with the alphaX beta-propeller and the beta2 vWFA domain (1, 8). In the inactive state, the heterodimer flexes in the center at the alphaX thigh and calf domains and beta2 I-EGF domains, impeding access to adhesion sites (1). The 1088 aa human alphaX/CD11c ECD shares 70‑76% aa sequence identity with mouse, rat and canine alphaX while the 678 aa human beta2/CD18 ECD shares 81‑83% aa sequence identity with mouse, rat, cow, dog, goat, sheep, and pig beta2. Potential alphaX isoforms containing 719 and 725 aa (as compared to full-length 1163 aa alphaX) lack the vWFA domain and the N-terminus. Active alphaX beta2 shares some adhesion partners with alphaM beta2/CD11b/CD18, including complement opsonin fragment iC3b, ICAMs, vWF and fibrinogen, and is expressed on many of the same cells (4‑11). However, alphaM beta2 activity is often constitutive, while alphaX beta2 activity requires cell activation (4‑7). alphaX beta2 also binds osteopontin, Thy-1, plasminogen, heparin, and proteins with abnormally exposed acidic residues (11‑16). The adhesion events are important for proliferation, degranulation, chemotactic migration, and phagocytosis of complement-opsonized particles (5, 6, 9, 11, 12, 16). Mutations of beta2, especially in the vWFA domain, cause leukocyte adhesion deficiency (LAD-1) and susceptibility to bacterial infections (17).