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,
Departments of
*
Dermatology and
Immunology and
Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan
Toll-like receptors (TLRs) are mammalian homologues of the
Drosophila Toll receptors and are thought to have roles
in innate recognition of bacteria. We demonstrated that TLR 2, 4, 6,
and 8 but not TLR5 were expressed on mouse bone marrow-derived mast
cells (BMMCs). Using BMMCs from the genetically TLR4-mutated strain
C3H/HeJ, we demonstrated that functional TLR4 was required for a full
responsiveness of BMMCs to produce inflammatory cytokines (IL-1
,
TNF-
, IL-6, and IL-13) by LPS stimulation. TLR4-mediated stimulation
of mast cells by LPS was followed by activation of NF-
B but not by
stress-activated protein kinase/c-Jun NH2-terminal
kinase signaling. In addition, in the cecal ligation and
puncture-induced acute septic peritonitis model, we demonstrated that
genetically mast cell-deficient W/Wv mice that
were reconstituted with TLR4-mutated BMMCs had significantly higher
mortality than W/Wv mice reconstituted with
TLR4-intact BMMCs. Higher mortality of TLR4-mutated BMMC-reconstituted
W/Wv mice was well correlated with defective
neutrophil recruitment and production of proinflammatory cytokines in
the peritoneal cavity. Taken together, these observations provide
definitive evidence that mast cells play important roles in exerting
the innate immunity by releasing inflammatory cytokines and recruitment
of neutrophils after recognition of enterobacteria through TLR4 on mast
cells.
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S. Okumura, J.-i. Kashiwakura, H. Tomita, K. Matsumoto, T. Nakajima, H. Saito, and Y. Okayama Identification of specific gene expression profiles in human mast cells mediated by Toll-like receptor 4 and Fc{epsilon}RI Blood, October 1, 2003; 102(7): 2547 - 2554. [Abstract] [Full Text] [PDF]
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S. Munoz, R. Hernandez-Pando, S. N. Abraham, and J. A. Enciso Mast Cell Activation by Mycobacterium tuberculosis: Mediator Release and Role of CD48 J. Immunol., June 1, 2003; 170(11): 5590 - 5596. [Abstract] [Full Text] [PDF]
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J. D. Schilling, S. M. Martin, C. S. Hung, R. G. Lorenz, and S. J. Hultgren Toll-like receptor 4 on stromal and hematopoietic cells mediates innate resistance to uropathogenic Escherichiacoli PNAS, April 1, 2003; 100(7): 4203 - 4208. [Abstract] [Full Text] [PDF]
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D. Skokos, H. G. Botros, C. Demeure, J. Morin, R. Peronet, G. Birkenmeier, S. Boudaly, and S. Mecheri Mast Cell-Derived Exosomes Induce Phenotypic and Functional Maturation of Dendritic Cells and Elicit Specific Immune Responses In Vivo J. Immunol., March 15, 2003; 170(6): 3037 - 3045. [Abstract] [Full Text] [PDF]
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J. D. McCurdy, T. J. Olynych, L. H. Maher, and J. S. Marshall Cutting Edge: Distinct Toll-Like Receptor 2 Activators Selectively Induce Different Classes of Mediator Production from Human Mast Cells J. Immunol., February 15, 2003; 170(4): 1625 - 1629. [Abstract] [Full Text] [PDF]
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A. Genovese, G. Borgia, L. Bjorck, A. Petraroli, A. de Paulis, M. Piazza, and G. Marone Immunoglobulin Superantigen Protein L Induces IL-4 and IL-13 Secretion from Human Fc{varepsilon}RI+ Cells Through Interaction with the {kappa} Light Chains of IgE J. Immunol., February 15, 2003; 170(4): 1854 - 1861. [Abstract] [Full Text] [PDF]
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K. K. Yang, B. G. Dorner, U. Merkel, B. Ryffel, C. Schutt, D. Golenbock, M. W. Freeman, and R. S. Jack Neutrophil Influx in Response to a Peritoneal Infection with Salmonella Is Delayed in Lipopolysaccharide-Binding Protein or CD14-Deficient Mice J. Immunol., October 15, 2002; 169(8): 4475 - 4480. [Abstract] [Full Text] [PDF]
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A. Masuda, Y. Yoshikai, K. Aiba, and T. Matsuguchi Th2 Cytokine Production from Mast Cells Is Directly Induced by Lipopolysaccharide and Distinctly Regulated by c-Jun N-Terminal Kinase and p38 Pathways J. Immunol., October 1, 2002; 169(7): 3801 - 3810. [Abstract] [Full Text] [PDF]
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S. E. Applequist, R. P. A. Wallin, and H.-G. Ljunggren Variable expression of Toll-like receptor in murine innate and adaptive immune cell lines Int. Immunol., September 1, 2002; 14(9): 1065 - 1074. [Abstract] [Full Text] [PDF]
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 J. Caamano and C. A. Hunter NF-{kappa}B Family of Transcription Factors: Central Regulators of Innate and Adaptive Immune Functions Clin. Microbiol. Rev., July 1, 2002; 15(3): 414 - 429. [Abstract] [Full Text] [PDF]
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K. Dabbagh, M. E. Dahl, P. Stepick-Biek, and D. B. Lewis Toll-Like Receptor 4 Is Required for Optimal Development of Th2 Immune Responses: Role of Dendritic Cells J. Immunol., May 1, 2002; 168(9): 4524 - 4530. [Abstract] [Full Text] [PDF]
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J. A. Boyce, E. A. Mellor, B. Perkins, Y.-C. Lim, and F. W. Luscinskas Human mast cell progenitors use alpha 4-integrin, VCAM-1, and PSGL-1 E-selectin for adhesive interactions with human vascular endothelium under flow conditions Blood, April 15, 2002; 99(8): 2890 - 2896. [Abstract] [Full Text] [PDF]
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V. Supajatura, H. Ushio, A. Wada, K. Yahiro, K. Okumura, H. Ogawa, T. Hirayama, and C. Ra Cutting Edge: VacA, a Vacuolating Cytotoxin of Helicobacter pylori, Directly Activates Mast Cells for Migration and Production of Proinflammatory Cytokines J. Immunol., March 15, 2002; 168(6): 2603 - 2607. [Abstract] [Full Text] [PDF]
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E. A. Mellor, K. F. Austen, and J. A. Boyce Cysteinyl Leukotrienes and Uridine Diphosphate Induce Cytokine Generation by Human Mast Cells Through an Interleukin 4-regulated Pathway that Is Inhibited by Leukotriene Receptor Antagonists J. Exp. Med., March 4, 2002; 195(5): 583 - 592. [Abstract] [Full Text] [PDF]
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