Absence of Fc(epsilon)RI alpha chain results in upregulation of Fc gamma RIII-dependent mast cell degranulation and anaphylaxis - Evidence of competition between Fc(epsilon)RI and Fc gamma RIII for limiting amounts of FcR beta and gamma chains
Absence of Fc(epsilon)RI alpha chain results in upregulation of Fc gamma RIII-dependent mast cell degranulation and anaphylaxis - Evidence of competition between Fc(epsilon)RI and Fc gamma RIII for limiting amounts of FcR beta and gamma chains
复制标题
DOI：
10.1172/jci119256
复制
发表时间：
1997-03-01
影响因子：
15.9
通讯作者：
Kinet, JP
中科院分区：
文献类型：
--
作者：
Dombrowicz, D;Flamand, V;Kinet, JP
在小鼠肥大细胞中，Fc(epsilon)RI和Fc γ RIII都是α - β - γ - 2四聚体复合物，其中不同的α链赋予IgE或IgG配体识别，而信号通路FcR β和γ链是相同的。我们主要使用无创技术（体温变化，染料外渗）来评估非麻醉野生型Fc(epsilon)RI α链-/-和FcR γ链-/-小鼠的全身过敏反应。我们证实，小鼠的全身性过敏反应主要通过IgG(1)和Fc γ RIII介导，我们提供了直接证据，证明这些反应反映了Fc γ RIII的激活，而不是Fc γ RI。此外，我们发现Fc γ RIII依赖性反应在正常小鼠中比在同源肥大细胞缺陷Kit(W)/Kit（W-v）小鼠中更强烈，表明Fc γ RIII反应具有肥大细胞依赖性和非依赖性成分。最后，我们证明了Fc(epsilon)RI α链-/-小鼠中Fc γ RIII细胞表面表达的上调与Fc γ RIII α链与FcR β和γ链的增加相关，并与Fc γ RIII依赖性肥大细胞脱颗粒和全身过敏反应增强相关。因此，Fc(epsilon)RI α链-/-小鼠的表型表明，Fc(epsilon)RI和Fc gamma RIII的表达受到FcR β链和gamma链可用性的限制，并且在正常小鼠中，一种受体（Fc(epsilon)RI）表达的变化可能影响依赖于另一种受体（Fc gamma RIII）的功能反应的表达。
In mouse mast cells, both Fc(epsilon)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, 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 gamma RIII-dependent responses are more intense in normal than in congenic mast cell-deficient Kit(W)/Kit(W-v) mice, indicating that Fc gamma RIII responses have mast cell-dependent and -independent components. Finally, we demonstrate that the upregulation 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 Fc(epsilon)RI alpha chain -/- mice suggests 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 mice, changes in the expression of one receptor (Fc(epsilon)RI) may influence the expression of functional responses dependent on the other (Fc gamma RIII).