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* Unité d’Allergologie Moléculaire et Cellulaire, Département d’Immunologie, Institut Pasteur, Paris, France;
Institut National de la Santé et de la Recherche Médicale, Unité 760, Paris, France;
Institut National de la Santé et de la Recherche Médicale, Unité 567, Institut Cochin, Paris, France; and
Laboratoire de Biotechnologies et Pharmacologie Génétique Appliquées, Ecole Normale Supérieure, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8113, Cachan, France
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 Fc
RIIIA and were negatively regulated by FcRIIB. We found that a moderate FcRIIB-dependent negative regulation, due not to a higher FcRIIIA/FcRIIB 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, and the Fondation Recherche Médicale (Program Défis de la Recherche en Allergologie). K.R. was supported by the Ministère de l’Education Nationale, de la Recherche et de la Technologie, C.S. by Danone-Vitapole, and A.R.D. by Sanofi Synthelabo.
2 Address correspondence and reprint requests to Dr. Marc Daëron, Unité d’Allergologie Moléculaire et Cellulaire, Département d’Immunologie, Institut Pasteur, 25 rue du Docteur Roux, 75015 Paris, France. E-mail address: daeron{at}pasteur.fr
3 Abbreviations used in this paper: SCF, stem cell factor; BMMC, bone marrow-derived mast cell; wt, wild type; MAR, mouse anti-rat; GAM, goat anti-mouse; GAR, goat anti-rabbit; RAM, rabbit anti-mouse; PCMC, peritoneal cell-derived mast cell; PAR, protease-activated receptor; TX100, Triton X-100; mMCP, murine MCP; LT, leukotriene.
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