Functionality of the IgA Fc receptor (FcαR, CD89) is down-regulated by extensive engagement of FcɛRI

Besides mast cells and basophils, the high-affinity IgE Fc receptor (FcɛRI) is exclusively expressed on certain FcαR (IgA Fc receptor)-expressing immune cells such as neutrophils in allergic patients. Transfected rat basophilic leukemia cell line (RBL-2H3) co-expressing FcɛRI and FcαR was analyzed for effects of simultaneous receptor engagement by their specific antibodies on degranulation and signaling. Whereas supraoptimal FcɛRI engagement decreased degranulation, which is known as a bell-shaped dose–response curve, such inhibitory effect was not observed with FcαR engagement. However, simultaneous engagement of FcɛRI and FcαR showed that supraoptimal FcɛRI engagement down-regulates FcαR-mediated degranulation. This inhibition was associated with extensive phosphorylation of inositol polyphosphate 5′-phosphatase SHIP1 and FcɛRIβ, and reversed by adding actin-depolymerizing drug, latrunculin B. The results suggest an endogenous mechanism by which FcαR functionality is down-regulated in an ‘allergic environment’ where FcɛRI is co-expressed and extensively cross-linked on FcαR-expressing effector cells.