ABSENCE OF FC(EPSILON)RI ALPHA-CHAIN RESULTS IN UP-REGULATION OF FC-GAMMA-RIII-DEPENDENT MAST-CELL DEGRANULATION AND ANAPHYLAXIS - EVIDENCEOF COMPETITION BETWEEN FC(EPSILON)RI AND FC-GAMMA-RIII FOR LIMITING AMOUNTS OF FCR-BETA AND FCR-GAMMA CHAINS

In mouse mast cells, both Fc(epsilon)RI and Fc gamma RIII are alpha be ta gamma 2 tetrameric complexes in which different alpha chains confer IgE or IgG ligand recognition while the signaling FcR beta and gamma chains are identical. We used primarily noninvasive techniques (change s in body temperature, dye extravasation) to assess systemic anaphylac tic responses in nonanesthetized wild-type, Fc(epsilon)RI alpha chain -/- and FcR gamma chain -/- mice. We confirm that systemic anaphylaxis in mice can be mediated largely through IgG(1) and Fc gamma RIII and we provide direct evidence that these responses reflect activation of Fc gamma RIII rather than Fc gamma RI. Furthermore, we show that Fc ga mma RIII-dependent responses are more intense in normal than in congen ic mast cell-deficient Kit(W)/Kit(W-v) mice, indicating that Fc gamma RIII responses have mast cell-dependent and -independent components. F inally, we demonstrate that the upregulation of cell surface expressio n of Fc gamma RIII seen in Fc(epsilon)RI alpha chain -/- mice correspo nds to an increased association of Fc gamma RIII alpha chains with FcR beta and gamma chains and is associated with enhanced Fc gamma RIII-d ependent mast cell degranulation and systemic anaphylactic responses. Therefore, the phenotype of the Fc(epsilon)RI alpha chain -/- mice sug gests that expression of Fc(epsilon)RI and Fc gamma RIII is limited by availability of the FcR beta and gamma chains and that, in normal mic e, changes in the expression of one receptor (Fc(epsilon)RI) may influ ence the expression of functional responses dependent on the other (Fc gamma RIII).