lewis-x-antigen and Hepatitis

Substantial evidence indicates that inflammation is a critical component of tumor progression. Hepatocellular carcinoma (HCC) is usually derived from inflamed cirrhotic liver with extensive leukocyte infiltration. Neutrophils are the common inflammatory infiltrate in tumors, but their nature and regulation in human cancers remain elusive.. A total of 238 HCC patients were enrolled randomly. Immunohistochemistry and SuperArray Real-Time PCR were used to analyze the distribution and clinical relevance of neutrophils in different microanatomical areas. The regulation and function of neutrophils were assessed by both in vitro and in vivo studies.. Neutrophils were enriched predominantly in peritumoral stroma of HCC tissues and their levels could serve as a powerful predictor for poor survival in HCC patients. Proinflammatory IL-17 is a critical mediator of the recruitment of neutrophils into peritumoral stroma of HCC tissues by epithelial cell-derived CXC chemokines. The accumulated peritumoral neutrophils were the major source of matrix metalloproteinase-9 in HCC tissues; this secreted protein stimulated proangiogenic activity in hepatoma cells. Accordingly, high infiltration of peritumoral neutrophils was positively correlated with angiogenesis progression at tumor-invading edge of HCC patients. Furthermore, we found that selective depletion of neutrophils effectively inhibited tumor angiogenesis and growth, in vivo.. These data provide direct evidence supporting the critical role of neutrophils in human tumor progression and reveal a fine-tuned collaborative action between cancer cells and immune cells in distinct tumor milieu, which reroutes the inflammatory response into a tumor-promoting direction.

Topics: Carcinoma, Hepatocellular; Disease Progression; Epithelial Cells; Fucosyltransferases; Hepatitis; Humans; Interleukin-17; Lewis X Antigen; Liver Cirrhosis; Liver Neoplasms; Matrix Metalloproteinase 9; Neovascularization, Pathologic; Neutrophils; Predictive Value of Tests; Signal Transduction; Survival Rate; Vascular Endothelial Growth Factor A

A carbohydrate antigen, sialyl Lewis X (SLEX), is an inflammation-associated liver cell antigen, which is increasingly expressed as histological diagnosis progresses. A solid phase radioimmunoassay was developed to determine the plasma levels of this substance which were found to be elevated in about 70% of patients with liver disease, with no significant differences among disease groups. Although the plasma levels of SLEX were not directly correlated with the degree of hepatic SLEX expression, the abnormal values were only found in cases with hepatic SLEX expression. Cirrhotic patients with and without hepatocellular carcinoma had comparable values. Plasma levels of SLEX decreased significantly in chronic hepatitis patients successfully treated with IFN, but not in those without a favourable clinical response. Plasma SLEX was carried by some macromolecules with chromatographic and buoyant properties of mucin-type glycoproteins, and others of non-mucin type. These observations suggested that (i) the plasma levels of SLEX increase significantly but non-specifically in liver diseases, (ii) liver cells in the inflammatory lesion are probably the origin of the SLEX-active glycoproteins in the peripheral circulation, (iii) both the increased hepatic synthesis and impaired secretion of the SLEX-positive glycoproteins might be related to the tissue expression and plasma levels of SLEX, and (iv) plasma SLEX might be a useful marker to evaluate the activity of inflammatory liver disease in individual patients and to monitor their treatment.

Topics: Adult; Chronic Disease; Female; Glycoproteins; Hepatitis; Humans; Interferons; Lewis X Antigen; Liver Diseases; Liver Function Tests; Male; Middle Aged

The hepatocellular expression of the carbohydrate antigen sialyl monomeric Lewis X (SMLex) and sialyl oligomeric Lewis X(SOLex) in chronic hepatitis was examined using specific monoclonal antibodies. Both of these sialyl Lewis X (SLex) antigens were membranously expressed in chronic hepatitis in spite of their absence in normal liver. Although SMLex was detected in mild hepatic inflammation, the expression of SOLex was associated only with moderate to severe necroinflammation. Hepatocellular expression of these antigens increased significantly as histological diagnosis advanced. Chronological observation also showed the change of SLex expression according to the histological change. The present observations suggest that hepatocellular SLex is a novel histological marker with a close correlation to the severity of necroinflammation in chronic hepatitis.

Topics: Biomarkers; Chronic Disease; Glycolipids; Hepatitis; Hepatitis, Chronic; Humans; Lewis X Antigen; Liver; Necrosis; Reference Values

The expression of a carbohydrate antigen, sialyl oligomeric Lewis X (SOLex), by Kupffer cells was examined in liver biopsy specimens from patients with chronic hepatitis. The antigen was expressed by Kupffer cells from these patients but not by those from normal controls. Expression of the antigen did not correlate with the histological type of chronic hepatitis, nor with SOLex expression in liver cells, which did correlate with severity of hepatic necrosis and inflammation. Treatment of patients with interferon-alpha increased SOLex expression by Kupffer cells, but not by liver cells, which suggests different means of regulation of SOLex expression in these two cell types. SOLex and HLA class II antigens were expressed simultaneously by Kupffer cells. Expression of SOLex by Kupffer cells (HLA class II antigen-positive) and liver cells (HLA class I antigen-positive) suggests a possible autoimmune response against this carbohydrate antigen in chronic hepatitis.

Topics: Adult; Chronic Disease; Glycolipids; Hepatitis; Hepatitis, Chronic; HLA Antigens; Humans; Immunoenzyme Techniques; Kupffer Cells; Lewis X Antigen; Liver; Male; Middle Aged