Mancardi David A, Iannascoli Bruno, Hoos Sylviane, England Patrick, Daëron Marc, Bruhns Pierre
Département d'Immunologie, Unité d'Allergologie Moléculaire et Cellulaire, Paris, France.
J Clin Invest. 2008 Nov;118(11):3738-50. doi: 10.1172/JCI36452. Epub 2008 Oct 23.
FcgammaRIV is a recently identified mouse activating receptor for IgG2a and IgG2b that is expressed on monocytes, macrophages, and neutrophils; herein it is referred to as mFcgammaRIV. Although little is known about mFcgammaRIV, it has been proposed to be the mouse homolog of human FcgammaRIIIA (hFcgammaRIIIA) because of high sequence homology. Our work, however, has revealed what we believe to be new properties of mFcgammaRIV that endow this receptor with a previously unsuspected biological significance; we have shown that it is a low-affinity IgE receptor for all IgE allotypes. Although mFcgammaRIV functioned as a high-affinity IgG receptor, mFcgammaRIV-bound monomeric IgGs were readily displaced by IgE immune complexes. Engagement of mFcgammaRIV by IgE immune complexes induced bronchoalveolar and peritoneal macrophages to secrete cytokines, suggesting that mFcgammaRIV may be an equivalent of human FceRI(alphagamma), which is expressed by macrophages and neutrophils and especially in atopic individuals, rather than an equivalent of hFcgammaRIIIA, which has no affinity for IgE. Using mice lacking 3 FcgammaRs and 2 FceRs and expressing mFcgammaRIV only, we further demonstrated that mFcgammaRIV promotes IgE-induced lung inflammation. These data lead us to propose a mouse model of IgE-induced lung inflammation in which cooperation exists between mast cells and mFcgammaRIV-expressing lung cells. We therefore suggest that a similar cooperation may occur between mast cells and hFceRI-expressing lung cells in human allergic asthma.
FcγRIV是最近发现的一种小鼠IgG2a和IgG2b激活受体，表达于单核细胞、巨噬细胞和中性粒细胞上；在此将其称为mFcγRIV。尽管对mFcγRIV了解甚少，但由于序列高度同源，有人提出它是人类FcγRIIIA（hFcγRIIIA）的小鼠同源物。然而，我们的研究揭示了我们认为是mFcγRIV的新特性，这些特性赋予了该受体前所未有的生物学意义；我们已经表明，它是所有IgE同种异型的低亲和力IgE受体。尽管mFcγRIV作为高亲和力IgG受体发挥作用，但mFcγRIV结合的单体IgG很容易被IgE免疫复合物取代。IgE免疫复合物与mFcγRIV结合可诱导支气管肺泡和腹腔巨噬细胞分泌细胞因子，这表明mFcγRIV可能相当于人类FceRI（αγ），后者由巨噬细胞和中性粒细胞表达，尤其是在特应性个体中，而不是相当于对IgE无亲和力的hFcγRIIIA。使用仅缺失3种FcγR和2种FceR并表达mFcγRIV的小鼠，我们进一步证明mFcγRIV促进IgE诱导的肺部炎症。这些数据使我们提出一种IgE诱导的肺部炎症小鼠模型，其中肥大细胞与表达mFcγRIV的肺细胞之间存在协同作用。因此，我们认为在人类过敏性哮喘中，肥大细胞与表达hFceRI的肺细胞之间可能也会发生类似的协同作用。
