Functionality of the IgA Fc receptor (FcalphaR, CD89) is down-regulated by extensive engagement of FcepsilonRI.

Abstract

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.

• Authors: Takashi Matsui, Satoshi Nunomura, Toshibumi Shimokawa, Tetsuro Yoshimaru, Chisei Ra
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 129 Issue 1 Pg. 155-62 (Oct 2008) ISSN: 1521-7035 [Electronic] United States
• PMID: 18700185 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Antigens, CD
• Bridged Bicyclo Compounds, Heterocyclic
• Fc(alpha) receptor
• Receptors, Fc
• Receptors, IgE
• Thiazolidines
• Phosphoric Monoester Hydrolases
• Inositol Polyphosphate 5-Phosphatases
• INPP5D protein, human
• Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
• latrunculin B

Topics

• Actins (metabolism)
• Animals
• Antigens, CD (immunology, metabolism)
• Bridged Bicyclo Compounds, Heterocyclic (pharmacology)
• Cell Degranulation (drug effects)
• Cell Line, Tumor
• Down-Regulation
• Humans
• Inositol Polyphosphate 5-Phosphatases
• Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
• Phosphoric Monoester Hydrolases (immunology, metabolism)
• Phosphorylation
• Rats
• Receptors, Fc (immunology, metabolism)
• Receptors, IgE (immunology, metabolism)
• Thiazolidines (pharmacology)