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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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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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