Article Figures & Data
Figures
- FIGURE 1.
Chemokine and chemokine receptor expression in the liver. Immunohistochemical peroxidase stains for IP-10 in both normal (a) and hepatitis C cirrhotic liver (b) (magnification, ×100) showing expression within sinusoidal endothelium (SE) in the hepatocyte lobule. Staining of sinusoidal endothelium is increased in the hepatitis C-infected liver compared with normal. IP-10 is selectively expressed on sinusoidal endothelium, and its expression is increased in the hepatitis C-infected liver. Mig is expressed by vascular endothelium in normal liver (c) and in hepatitis C cirrhotic liver (d) (magnification, ×100), where its expression on sinusoidal endothelium is increased. As well as expression on portal vein (PV), it is expressed within the wall (subendothelial layer) of small arteries (HA) within the liver. MIP-1β is expressed mainly by portal vein endothelium within the portal tracts (e; alkaline phosphatase anti-alkaline phosphatase fast red stain; magnification, ×200). The chemokine receptor CXCR3 (for IP-10 and Mig) is expressed on the majority of liver infiltrating lymphocytes, here shown within hepatitis C cirrhotic liver (magnification, ×200) using a peroxidase method (f). TNF-α is detected in mononuclear cells in portal tracts within hepatitis C-infected liver, and there is also weak staining in hepatocytes (g). Kupffer cells in the sinusoids in hepatic lobules were strongly positive for TNF-α in hepatitis C-infected liver (h).
- FIGURE 2.
Chemokine receptor expression by peripheral blood- and liver-derived T cells. Two-color flow cytometry of T cells from normal (N) liver (n = 6) and normal peripheral blood (N PB, n = 6) and hepatitis C cirrhotic (HCV) liver (n = 8) compared with autologous peripheral blood (HCV PB) T cells (n = 8). Data shown for liver-derived T cells is that using the collagenase digestion method. T cells were gated by forward and side scatter characteristics and by their expression of CD3. A, Mean CXCR3 staining intensity (MCF − MCF of irrelevant Ab ± SEM) on T cells and flow cytometry data (dot plot) for an individual patient’s peripheral blood- and liver-derived T cells is representative of all the patients studied. Liver-derived T cells expressed higher levels of CXCR3 than peripheral blood T cells (p = 0.0039 for hepatitis C patients, p = 0.03 for normal donors). B, The percentage of T cells expressing chemokine receptor CCR5 (mean ± SEM) and data for a single representative patient. A higher percentage of liver T cells expressed CCR5 than peripheral blood T cells (p = 0.004 for HCV patients, p = 0.009 for normal donors).
- FIGURE 3.
CCR5 expression on memory (CD45RO+) T cells from peripheral blood (PB) and liver of patient with hepatitis C cirrhosis (n = 6). Three-color flow cytometry was performed by gating on CD3-positive cells. Tissue infiltrating CD45RO+ cells show increased expression of CCR5 than peripheral blood CD45RO+ cells (p = 0.03).
- FIGURE 4.
CCR3 expression on peripheral blood (PB)- and liver-derived T cells from a patient with hepatitis C cirrhosis. Two-color flow cytometry was performed by gating on CD3-positive cells. Figures in quadrants represent percentage of T cells expressing CCR3. Data is representative of three paired patient samples studied.
- FIGURE 5.
IP-10 and Mig expression and secretion from HSEC isolated from normal liver. Cells were cultured until confluent and then stimulated for 24 h in media containing no cytokines or proinflammatory cytokines either alone or in combination (lanes 1–8). A, IP-10 and Mig protein was measured by ELISA, and the graph represents mean data of three replicates (±SD). One experiment representative of three separate experiments is shown. B, IP-10 and Mig gene expression (mRNA) in HSEC measured by RT-PCR.
Tables
- Table I.
Chemokine expression by liver vascular endothelium in normal and hepatitis C cirrhotic livera
MIP-1α MIP-1β Mig IP-10 Normal liver n = 7 n = 8 n = 8 n = 8 Sinusoidal endothelium 0.42 (0–1) 1.0 (0–2) 1.4 (1–2) 0.38 (0–1) Portal vein 2.43 (2–3) 2.50 (2–3) 0.87 (0–2) 0 (0) Hepatic vein 0.57 (0–1) 0.75 (0–1) 0.57 (0–1) 0 (0) Hepatitis C cirrhotic liver n = 7 n = 14 n = 14 n = 16 Sinusoidal endothelium 0.86 (0–1) 1.1 (0–2) 2.6 (2–3)* 1.4 (0–3)** Portal vein 2.7 (2–3) 2.7 (2–3) 1.5 (0–2) 0 (0) Hepatic vein 0.7 (0–1) 0.85 (0–2) 0.4 (0–1) 0 (0) -
a Table summarizes results of immunohistochemistry with staining intensity scored as follows: 0 = absent, 1 = weak, 2 = moderate, and 3 = strong. Values represent overall mean staining intensity with range of individual scores in parentheses. Significant differences were seen between hepatitis C cirrhotic and normal liver for Mig (∗, p = 0.002, Mann-Whitney U test) and IP-10 expression (∗∗, p = 0.015) on sinusoidal endothelium.
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