ORIGINAL ARTICLEExpression of CD163 in the liver of patients with viral hepatitis
Introduction
Macrophages, in particular the activated macrophages, produce a variety of proinflammatory mediators and play a role in the maintenance of the inflammatory milieu in different inflammatory conditions, such as hepatitis [1], [12], arthritis [10], ulcerative colitis [11], and arteriosclerosis [14]. Indeed, cells of monocyte/macrophage lineages heavily infiltrate in the target organs in these pathologic conditions. However, little is known about the role of macrophages or activated macrophages in the pathogenesis of these inflammatory diseases. Study of activated macrophages has now become possible, because an immunologic marker of activated macrophages has recently been described. CD163, a cell surface glycoprotein of the scavenger receptor cysteine-rich family, is expressed in activated macrophages [7], [16], [17]. Some investigators have demonstrated that CD163-positive activated macrophages are located in the synovial membrane of joint tissues obtained from patients with rheumatoid arthritis [5], synovium in spondyloarthropathy [3], and coronary arteries in arteriosclerosis [14]. Moreover, a soluble form of CD163 (sCD163) has been characterized, and a methodology has been established that allows for its detection in the sera and other body fluids [9], [19]. Recently, we checked the sCD163 levels in the sera from patients affected by fulminant hepatic failure (FHF), acute hepatitis (AH), and chronic hepatitis (CH) [6]. Very high levels of sCD163 were detected in sera from patients with FHF, followed by AH and CH, indicating a relationship between the severity of hepatitis and the levels of serum sCD163. Moreover, a prognostic importance of soluble sCD163 has been reported in patients with FHF [6]. However, the expression of CD163 in the liver tissue of patients with hepatitis has not yet been investigated. We presume that CD163 is expressed in the liver of patients affected by different types of hepatitis. In fact, there is a fundamental difference regarding the nature of infiltrating cells in the liver of patients with AH and CH. In the liver tissues obtained from patients with AH, both lymphocytes and phagocytic macrophages are detected. However, lymphocytes are localized predominantly in the liver tissues of patients with CH. This led us to speculate that activated liver macrophages (i.e. Kupffer cells) might have dominant roles in the pathogenesis of AH.
To gain some insight into this topic, we investigated CD163-positive cells in the liver of patients with AH and CH. The frequencies of CD163-positive cells were higher in liver tissues obtained from patients with AH compared to those with CH. Then, the cells in the liver tissue co-expressing CD163 and lymphocytes or macrophages or endothelial cells or liver stellate cells were determined using dual-color immunostaining.
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Patients
Liver specimens were obtained from 5 patients with AH (mean age; 46 years), from 23 patients with CH (mean age; 51 years), and from 1 patient with fatty liver. Table 1 gives the clinical profiles of these patients on admission. The levels of total bilirubin, alanine, and aspirate aminotransferase in the sera were significantly higher in patients with AH compared to those with CH. Two, 2, and 1 patient with AH were infected with hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C
Localization of CD163-positive cells in the liver tissues
Cells expressing CD163 were detected in all liver specimens, although the numbers of CD163-expressing cells differed considerably among different patients. Representative staining patterns of CD163 in the liver specimens obtained from patients with AH and CH are shown in Fig. 1. The expression of CD163 was detected in the nonparenchymal cells of the hepatic lobules and in portal areas in both AH and CH. Signals for CD163 were not detected in hepatocytes or biliary epithelial cells.
As shown in
Discussion
Lymphocytes, in particular cytotoxic T cells (CTL), are located in the liver tissues of patients with CH, and CTL is presumed to play a dominant role in the destruction of hepatocytes in CH [15]. Although CTL also induces the destruction of hepatocytes in patients with AH, other immunocytes might be involved in this process in AH. In addition to lymphocytes, macrophages and in particular phagocytic macrophages are accumulated in the liver tissues of patients with AH [8]. Interestingly, the
Acknowledgment
The expert technical assistance of Kenji Tanimoto and Satomi Yamanaka is greatly appreciated.
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