Essential role of MD-2 in B-cell responses to lipopolysaccharide and Toll-like receptor 4 distribution.
Toll-like receptor 4 (TLR4) mediates lipopolysaccharide (LPS) signaling in a variety of cell types. MD-2 is associated with the extracellular domain of TLR4 and augments TLR4-dependent LPS responses in vitro. Moreover, mice lacking MD-2 (MD-2(-/-)) do not respond to LPS, survive endotoxin shock, and are susceptible to Salmonella typhimurium infection. Here, we further show that B cells lacking MD-2 do not up-regulate CD23 in response to LPS. TLR4 predominantly resides in the Golgi apparatus without MD-2. MD-2 is essential for LPS responses in vivo.
Miyake
Kensuke
K
Division of Infectious Genetics, The Institute of Medical Science, The University of Tokyo, Japan. kmiyake@ims.u-tokyo.ac.jp
Nagai
Yoshinori
Y
Akashi
Sachiko
S
Nagafuku
Masakazu
M
Ogata
Masato
M
Kosugi
Atsushi
A
D000818:Animals; D000954:Antigens, Surface / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques; D005347:Fibroblasts; D006056:Golgi Apparatus; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D011956:Receptors, Cell Surface / Q000235:genetics; D017455:Receptors, IgE / Q000096:biosynthesis; D012481:Salmonella Infections, Animal; D012486:Salmonella typhimurium / Q000472:pathogenicity; D015398:Signal Transduction; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015854:Up-Regulation
D000954:Antigens, Surface; C495377:LY96 protein, human; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D017455:Receptors, IgE; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors