Human FCAR/CD89 Alexa Fluor® 350‑conjugated Antibody

FCAR, also called Fc alpha RI or CD89, is a variably glycosylated 50‑100 kDa myeloid-specific type I transmembrane (TM) Fc receptor for IgA that is a member of the multichain immune recognition receptor (MIRR) family (1‑3). Human FCAR contains a 21 amino acid (aa) signal sequence and extracellular (ECD), TM and cytoplasmic domains of 206, 19 and 41 aa, respectively (4). Arg230 within the TM domain supports interaction with the ITAM-containing signaling subunit, FcR gamma, which contains a TM Asp (5‑7). Two ECD C2-type Ig-like domains (EC1 and 2) are oriented at right angles (8). Up to two molecules of FCAR can bind one molecule of serum IgA via EC1 (8). Many splice variants have been reported, but only two have been identified as proteins (9, 10). The a.2 form, which lacks 22 aa just prior to the TM domain, is exclusively expressed in alveolar macrophages. The a.3 form lacks EC2. FCAR binds monomeric, polymeric and secretory IgA, but does not mediate the barrier function of secretory IgA in mucosal epithelium (1‑3). Shedding and circulation of polymeric IgA/FCAR immune complexes has been reported (11). Circulating neutrophils, eosinophils, and monocytes express FCAR (12). Tissue expression of FCAR is mainly from neutrophils; FCAR is downregulated as monocytes differentiate to tissue macrophages (12). On neutrophils, a significant amount of FCAR lacks FcR gamma, but can still be endocytosed to early endosomes and recycled to the cell surface (5). Binding of serum IgA to FCAR is transient and anti-inflammatory, inhibiting IgG or IgE-induced degranulation (6). Sustained aggregation of FCAR results in inflammatory responses (6). FcR gamma signaling is required for these and for transport to late endosomes (5 - 7). Human FCAR shows 55‑58% aa identity with rat, horse and cow FCAR. No ortholog occurs in mouse. FCAR structure resembles the KIR/ILT/LIR/MIR family more than other IgA receptors, including pIgR, Fc alpha /μR, asialoglycoprotein receptor (ASGR1) and transferrin receptor (TfR) (1‑3).