MD-2 is required for the full responsiveness of mast cells to LPS but not to PGN.

To address the role played by MD-2 in mast cell recognition of LPS, we examined bone marrow-derived mast cells (BMMCs) from MD-2 gene-targeted mice. BMMCs from MD-2-/- mice showed impaired cytokine production (TNF-alpha, IL-6, IL-13, and IL-1beta) in response to LPS from Escherichia coli, but not to peptidoglycan (PGN) from Staphylococcus aureus. In a mast cell-dependent acute septic model, MD-2 deficiency of mast cell resulted in significantly higher mortality due to defective neutrophil recruitment and the production of cytokines in the peritoneal cavity, which was similar to mice with TLR4-deficient mast cells. The TLR2-dependent activation of skin mast cells by PGN was not altered by the absence of MD-2 in vivo. Collectively, MD-2 is essential for the recognition of LPS by TLR4 but not for that of PGN by TLR2 of mast cells.

Ushio H ，Nakao A ，Supajatura V ，Miyake K ，Okumura K ，Ogawa H ... -  《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》

Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity.

Supajatura V ，Ushio H ，Nakao A ，Akira S ，Okumura K ，Ra C ，Ogawa H ... -  《-》

Toll-like receptor 4-mediated activation of murine mast cells.

McCurdy JD ，Lin TJ ，Marshall JS 《JOURNAL OF LEUKOCYTE BIOLOGY》

Toll-like receptor 2 (TLR2) and TLR4 differentially activate human mast cells.

Varadaradjalou S ，Féger F ，Thieblemont N ，Hamouda NB ，Pleau JM ，Dy M ，Arock M ... -  《EUROPEAN JOURNAL OF IMMUNOLOGY》

Cooperation between toll-like receptor 2 and 4 in the brain of mice challenged with cell wall components derived from gram-negative and gram-positive bacteria.

Laflamme N ，Echchannaoui H ，Landmann R ，Rivest S ... -  《EUROPEAN JOURNAL OF IMMUNOLOGY》