Abstract
The role played by chemokines in regulating the selective recruitment of lymphocytes to different tissue compartments in disease is poorly characterized. In hepatitis C infection, inflammation confined to portal areas is associated with a less aggressive course, whereas T cell infiltration of the liver parenchyma is associated with progressive liver injury and cirrhosis. We propose a mechanism to explain how lymphocytes are recruited to hepatic lobules during bursts of necroinflammatory activity in chronic hepatitis C infection. We report here that lymphocytes infiltrating hepatitis C-infected liver express high levels of the chemokine receptors CCR5 and CXCR3. However, whereas the CCR5 ligands macrophage inflammatory protein-1alpha and -1beta were largely confined to vessels within portal tracts, the CXCR3 ligands IFN-inducible protein-10 and monokine-induced by IFN-gamma were selectively up-regulated on sinusoidal endothelium. In vitro, human hepatic sinusoidal endothelial cells secreted IFN-inducible protein-10 and monokine-induced by IFN-gamma in response to stimulation with IFN-gamma in combination with either IL-1 or TNF-alpha. This suggests that intrahepatic Th1 cytokines drive the increased expression of IFN-inducible protein-10 and monokine-induced by IFN-gamma and thereby promote the continuing recruitment of CXCR3-expressing T cells into the hepatic lobule in chronic hepatitis C infection.
Original language | English |
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Pages (from-to) | 6236-43 |
Number of pages | 8 |
Journal | Journal of Immunology |
Volume | 163 |
Issue number | 11 |
Publication status | Published - 1 Dec 1999 |
Keywords
- Cell Movement
- Chemokine CXCL10
- Chemokine CXCL9
- Chemokines
- Chemokines, CXC
- Endothelium, Vascular
- Hepatitis C, Chronic
- Humans
- Intercellular Signaling Peptides and Proteins
- Interferon-gamma
- Kupffer Cells
- Liver
- Portal Vein
- Receptors, CCR5
- Receptors, CXCR3
- Receptors, Chemokine
- T-Lymphocyte Subsets
- T-Lymphocytes
- Th1 Cells
- Th2 Cells
- Tissue Distribution
- Tumor Necrosis Factor-alpha