Functionality of the IgA Fc receptor (FcalphaR, CD89) is down-regulated by extensive engagement of FcepsilonRI.
Besides mast cells and basophils, the high-affinity IgE Fc receptor (FcepsilonRI) is exclusively expressed on certain FcalphaR (IgA Fc receptor)-expressing immune cells such as neutrophils in allergic patients. Transfected rat basophilic leukemia cell line (RBL-2H3) co-expressing FcepsilonRI and FcalphaR was analyzed for effects of simultaneous receptor engagement by their specific antibodies on degranulation and signaling. Whereas supraoptimal FcepsilonRI engagement decreased degranulation, which is known as a bell-shaped dose-response curve, such inhibitory effect was not observed with FcalphaR engagement. However, simultaneous engagement of FcepsilonRI and FcalphaR showed that supraoptimal FcepsilonRI engagement down-regulates FcalphaR-mediated degranulation. This inhibition was associated with extensive phosphorylation of inositol polyphosphate 5'-phosphatase SHIP1 and FcepsilonRIbeta, and reversed by adding actin-depolymerizing drug, latrunculin B. The results suggest an endogenous mechanism by which FcalphaR functionality is down-regulated in an 'allergic environment' where FcepsilonRI is co-expressed and extensively cross-linked on FcalphaR-expressing effector cells.
Matsui
Takashi
T
Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Itabashi-ku, Tokyo 173-8610, Japan.
Nunomura
Satoshi
S
Shimokawa
Toshibumi
T
Yoshimaru
Tetsuro
T
Ra
Chisei
C
D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011961:Receptors, Fc / Q000276:immunology / Q000378:metabolism*; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism*; D053778:Thiazolidines / Q000494:pharmacology
D000199:Actins; D015703:Antigens, CD; D019086:Bridged Bicyclo Compounds, Heterocyclic; C036832:Fc(alpha) receptor; D011961:Receptors, Fc; D017455:Receptors, IgE; D053778:Thiazolidines; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606430:INPP5D protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; C037068:latrunculin B