The hepatocyte as a microbial product-responsive cell.
Much research has focused on the responses to microbial products of immune cells such as monocytes, macrophages, and neutrophils. Although the liver is a primary response organ in various infections, relatively little is known about the antimicrobial responses of its major cell type, the hepatocyte. It is now known that the recognition of bacteria occurs via cell-surface proteins that are members of the Toll-like receptor (TLR) family. In addition, lipopolysaccharide (LPS) is bound by circulating LPS-binding protein (LBP) and presented to cell-surface CD14, which in turn interacts with TLR and transduces an intracellular signal. We investigated the CD14 and TLR2 responses of whole liver and isolated hepatocytes, and demonstrated that these cells can be induced to express the molecules necessary for responses to both Gram-positive and Gram-negative bacteria. Our findings may have clinical implications for pathological states such as sepsis.
Vodovotz
Y
Y
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Liu
S
S
McCloskey
C
C
Shapiro
R
R
Green
A
A
Billiar
T R
TR
D000209:Acute-Phase Proteins; D000818:Animals; D017951:Antigen Presentation; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D029721:Drosophila Proteins; D015870:Gene Expression / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D017403:In Situ Hybridization; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D000099231:Lipopolysaccharide-Binding Protein; C495343:Tlr2 protein, rat