Absence of Fcepsilon RI alpha Chain Results in Upregulation of Fc gamma RIII-dependent Mast Cell Degranulation and Anaphylaxis: Evidence of Competition between Fcepsilon RI and Fc gamma RIII for Limiting Amounts of FcR beta and gamma Chains


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Abstract

In mouse mast cells, both Fcepsilon RI and Fc gamma RIII are alpha beta 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 (changes in body temperature, dye extravasation) to assess systemic anaphylactic responses in nonanesthetized wild-type, Fcepsilon RI alpha chain -/- and FcR gamma chain -/- mice. We confirm that systemic anaphylaxis in mice can be mediated largely through IgG1 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 gamma RIII-dependent responses are more intense in normal than in congenic mast cell-deficient KitW/KitW-nu mice, indicating that Fc gamma RIII responses have mast cell-dependent and -independent components. Finally, we demonstrate that the up-regulation of cell surface expression of Fc gamma RIII seen in Fc epsilon RI alpha chain -/- mice corresponds to an increased association of Fc gamma RIII alpha chains with FcR beta and gamma chains and is associated with enhanced Fc gamma RIII-dependent mast cell degranulation and systemic anaphylactic responses. Therefore, the phenotype of the Fcepsilon RI alpha chain -/- mice suggests that expression of Fcepsilon RI and Fc gamma RIII is limited by availability of the FcR beta and gamma chains and that, in normal mice, changes in the expression of one receptor (Fcepsilon RI) may influence the expression of functional responses dependent on the other (Fc gamma RIII). (J. Clin. Invest. 1997. 99:915-925.)

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