Malbec Odile, Roget Karine, Schiffer Cécile, Iannascoli Bruno, Dumas Antoine Ribadeau, Arock Michel, Daëron Marc
Unité d'Allergologie Moléculaire et Cellulaire, Département d'Immunologie, Institut Pasteur, Paris, France.
J Immunol. 2007 May 15;178(10):6465-75. doi: 10.4049/jimmunol.178.10.6465.
Bone marrow-derived mast cells (BMMC) have been used extensively as a mast cell model. BMMC, however, are immature cells that have no known physiological equivalent in tissues. They do not respond to IgG immune complexes. They may therefore not be appropriate for studying the physiopathology of IgE-induced allergies or IgG-induced tissue-specific inflammatory diseases which both depend on mature mast cells. Resident peritoneal mast cells are a minor population of differentiated cells that are not readily purified. They, however, can be expanded in culture to generate large numbers of homogeneous cells. We show here that these peritoneal cell-derived mast cells (PCMC) are mature serosal-type mouse mast cells which retain most morphological, phenotypic, and functional features of peritoneal mast cells. Like peritoneal mast cells, PCMC respond to IgG Abs. IgG immune complex-induced responses depended on FcgammaRIIIA and were negatively regulated by FcgammaRIIB. We found that a moderate FcgammaRIIB-dependent negative regulation, due not to a higher FcgammaRIIIA/FcgammaRIIB ratio, but to a relatively inefficient use of the lipid phosphatase SHIP1, determines this property of PCMC. PCMC also respond to IgE Abs. IgE-induced PCMC responses, however, differed quantitatively and qualitatively from BMMC responses. PCMC secreted no or much lower amounts of lipid mediators, chemokines, and cytokines, but they contained and released much higher amounts of preformed granular mediators. PCMC, but not BMMC, also contained and, upon degranulation, released molecules with a potent proteolytic activity. These properties make PCMC a useful new model for understanding the physiopathology of mast cells in IgE- and IgG-dependent tissue inflammation.
骨髓来源的肥大细胞（BMMC）已被广泛用作肥大细胞模型。然而，BMMC是未成熟细胞，在组织中没有已知的生理等效物。它们对IgG免疫复合物无反应。因此，它们可能不适用于研究IgE诱导的过敏或IgG诱导的组织特异性炎症疾病的病理生理学，这两种疾病都依赖于成熟的肥大细胞。驻留腹膜肥大细胞是一小部分分化细胞，不易纯化。然而，它们可以在培养中扩增以产生大量同质细胞。我们在此表明，这些腹膜细胞来源的肥大细胞（PCMC）是成熟的浆膜型小鼠肥大细胞，保留了腹膜肥大细胞的大多数形态、表型和功能特征。与腹膜肥大细胞一样，PCMC对IgG抗体有反应。IgG免疫复合物诱导的反应依赖于FcγRIIIA，并受到FcγRIIB的负调节。我们发现，适度的FcγRIIB依赖性负调节，不是由于较高的FcγRIIIA/FcγRIIB比率，而是由于脂质磷酸酶SHIP1的相对低效利用，决定了PCMC的这一特性。PCMC也对IgE抗体有反应。然而，IgE诱导的PCMC反应在数量和质量上与BMMC反应不同。PCMC分泌的脂质介质、趋化因子和细胞因子很少或量很低，但它们含有并释放了大量预先形成的颗粒介质。PCMC而非BMMC还含有并在脱颗粒时释放具有强大蛋白水解活性的分子。这些特性使PCMC成为理解IgE和IgG依赖性组织炎症中肥大细胞病理生理学的有用新模型。
