Monocyte chemotactic protein-1, -2, and -3 are distinctively expressed in portal tracts and granulomata in primary biliary cirrhosis: Implications for pathologenesis

Koichi Tsuneyama, Kenichi Harada, Mitsue Yasoshima, Katsushi Hiramatsu, Charles R. Mackay, Ian R. Mackay, M. Eric Gershwin, Yasuni Nakanuma

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

The monocyte chemotactic proteins (MCPs) form a distinct structurally related subclass of C-C chemokines. MCPs select specific target cells due to binding to a distinct set of chemokine receptors and because of their effects on monocytes, and may participate in the process of granuloma formation during bacterial and/or mycobacterial infections. The aetiology of primary biliary cirrhosis (PBC) is still unclear, although bacterial infection and autoimmune processes have been implicated. In this study, the expression of three of the most potent monocyte chemoattractants, MCP-1, -2, and -3, was examined in patients with PBC and the data were compared with results for other liver diseases including primary sclerosing cholangitis (PSC), chronic viral hepatitis C, hepatic sarcoidosis, and normal liver. MCP-1 was expressed mainly in biliary epithelial cells of all liver specimens, irrespective of the cause of disease. Some mononuclear leukocytes in the portal tract expressed MCP-1 in all the disease groups examined and there were no significant differences in frequency between these groups. In contrast, more than 80% of PBC livers showed MCP-2- and MCP-3-positive mononuclear leukocyte infiltration in portal tracts, particularly around the bile ducts, whereas such cells were far less frequent in the other disease groups or in normal livers. Epithelioid granulomata of PBC patients contained MCP-2- and MCP-3-positive cells at their edge. In double staining experiments, more than 60% of the MCP-positive mononuclear cells co-expressed CD68, suggesting that a proportion of MCP-2- and MCP-3-positive cells are derived from monocytes. These monocytes expressing MCP-2 and MCP-3 may be responsible for the chemotactic activity of more monocytes. Such an expression pattern of MCP-1, -2 and -3 in portal tracts seems to be distinctive for PBC. This pattern underlines the importance of MCP-1, -2, and -3 in the recruitment of monocytes and possibly T lymphocytes into portal tracts, around the injured bile ducts, and into epithelioid granulomata in PBC. The data further implicate bacterial materials derived from bile in the overall pathogenesis of PBC.

Original languageEnglish (US)
Pages (from-to)102-109
Number of pages8
JournalJournal of Pathology
Volume193
Issue number1
DOIs
StatePublished - 2001

Fingerprint

Chemokine CCL8
Biliary Liver Cirrhosis
Chemokine CCL2
Granuloma
Chemokine CCL7
Monocytes
Monocyte Chemoattractant Proteins
Liver
Mononuclear Leukocytes
Bile Ducts
CC Chemokines
Sclerosing Cholangitis
Chemokine Receptors
Chemotactic Factors
Chronic Hepatitis C
Sarcoidosis
Bacterial Infections
Bile
Liver Diseases
Epithelial Cells

Keywords

  • Chemokine
  • Infection
  • MCP-1
  • MCP-2
  • MCP-3
  • Primary biliary cirrhosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Monocyte chemotactic protein-1, -2, and -3 are distinctively expressed in portal tracts and granulomata in primary biliary cirrhosis : Implications for pathologenesis. / Tsuneyama, Koichi; Harada, Kenichi; Yasoshima, Mitsue; Hiramatsu, Katsushi; Mackay, Charles R.; Mackay, Ian R.; Gershwin, M. Eric; Nakanuma, Yasuni.

In: Journal of Pathology, Vol. 193, No. 1, 2001, p. 102-109.

Research output: Contribution to journalArticle

Tsuneyama, Koichi ; Harada, Kenichi ; Yasoshima, Mitsue ; Hiramatsu, Katsushi ; Mackay, Charles R. ; Mackay, Ian R. ; Gershwin, M. Eric ; Nakanuma, Yasuni. / Monocyte chemotactic protein-1, -2, and -3 are distinctively expressed in portal tracts and granulomata in primary biliary cirrhosis : Implications for pathologenesis. In: Journal of Pathology. 2001 ; Vol. 193, No. 1. pp. 102-109.
@article{90ee948b40194980a3d1f22b988471ff,
title = "Monocyte chemotactic protein-1, -2, and -3 are distinctively expressed in portal tracts and granulomata in primary biliary cirrhosis: Implications for pathologenesis",
abstract = "The monocyte chemotactic proteins (MCPs) form a distinct structurally related subclass of C-C chemokines. MCPs select specific target cells due to binding to a distinct set of chemokine receptors and because of their effects on monocytes, and may participate in the process of granuloma formation during bacterial and/or mycobacterial infections. The aetiology of primary biliary cirrhosis (PBC) is still unclear, although bacterial infection and autoimmune processes have been implicated. In this study, the expression of three of the most potent monocyte chemoattractants, MCP-1, -2, and -3, was examined in patients with PBC and the data were compared with results for other liver diseases including primary sclerosing cholangitis (PSC), chronic viral hepatitis C, hepatic sarcoidosis, and normal liver. MCP-1 was expressed mainly in biliary epithelial cells of all liver specimens, irrespective of the cause of disease. Some mononuclear leukocytes in the portal tract expressed MCP-1 in all the disease groups examined and there were no significant differences in frequency between these groups. In contrast, more than 80{\%} of PBC livers showed MCP-2- and MCP-3-positive mononuclear leukocyte infiltration in portal tracts, particularly around the bile ducts, whereas such cells were far less frequent in the other disease groups or in normal livers. Epithelioid granulomata of PBC patients contained MCP-2- and MCP-3-positive cells at their edge. In double staining experiments, more than 60{\%} of the MCP-positive mononuclear cells co-expressed CD68, suggesting that a proportion of MCP-2- and MCP-3-positive cells are derived from monocytes. These monocytes expressing MCP-2 and MCP-3 may be responsible for the chemotactic activity of more monocytes. Such an expression pattern of MCP-1, -2 and -3 in portal tracts seems to be distinctive for PBC. This pattern underlines the importance of MCP-1, -2, and -3 in the recruitment of monocytes and possibly T lymphocytes into portal tracts, around the injured bile ducts, and into epithelioid granulomata in PBC. The data further implicate bacterial materials derived from bile in the overall pathogenesis of PBC.",
keywords = "Chemokine, Infection, MCP-1, MCP-2, MCP-3, Primary biliary cirrhosis",
author = "Koichi Tsuneyama and Kenichi Harada and Mitsue Yasoshima and Katsushi Hiramatsu and Mackay, {Charles R.} and Mackay, {Ian R.} and Gershwin, {M. Eric} and Yasuni Nakanuma",
year = "2001",
doi = "10.1002/1096-9896(2000)9999:9999<::AID-PATH725>3.0.CO;2-P",
language = "English (US)",
volume = "193",
pages = "102--109",
journal = "Journal of Pathology",
issn = "0022-3417",
publisher = "John Wiley and Sons Ltd",
number = "1",

}

TY - JOUR

T1 - Monocyte chemotactic protein-1, -2, and -3 are distinctively expressed in portal tracts and granulomata in primary biliary cirrhosis

T2 - Implications for pathologenesis

AU - Tsuneyama, Koichi

AU - Harada, Kenichi

AU - Yasoshima, Mitsue

AU - Hiramatsu, Katsushi

AU - Mackay, Charles R.

AU - Mackay, Ian R.

AU - Gershwin, M. Eric

AU - Nakanuma, Yasuni

PY - 2001

Y1 - 2001

N2 - The monocyte chemotactic proteins (MCPs) form a distinct structurally related subclass of C-C chemokines. MCPs select specific target cells due to binding to a distinct set of chemokine receptors and because of their effects on monocytes, and may participate in the process of granuloma formation during bacterial and/or mycobacterial infections. The aetiology of primary biliary cirrhosis (PBC) is still unclear, although bacterial infection and autoimmune processes have been implicated. In this study, the expression of three of the most potent monocyte chemoattractants, MCP-1, -2, and -3, was examined in patients with PBC and the data were compared with results for other liver diseases including primary sclerosing cholangitis (PSC), chronic viral hepatitis C, hepatic sarcoidosis, and normal liver. MCP-1 was expressed mainly in biliary epithelial cells of all liver specimens, irrespective of the cause of disease. Some mononuclear leukocytes in the portal tract expressed MCP-1 in all the disease groups examined and there were no significant differences in frequency between these groups. In contrast, more than 80% of PBC livers showed MCP-2- and MCP-3-positive mononuclear leukocyte infiltration in portal tracts, particularly around the bile ducts, whereas such cells were far less frequent in the other disease groups or in normal livers. Epithelioid granulomata of PBC patients contained MCP-2- and MCP-3-positive cells at their edge. In double staining experiments, more than 60% of the MCP-positive mononuclear cells co-expressed CD68, suggesting that a proportion of MCP-2- and MCP-3-positive cells are derived from monocytes. These monocytes expressing MCP-2 and MCP-3 may be responsible for the chemotactic activity of more monocytes. Such an expression pattern of MCP-1, -2 and -3 in portal tracts seems to be distinctive for PBC. This pattern underlines the importance of MCP-1, -2, and -3 in the recruitment of monocytes and possibly T lymphocytes into portal tracts, around the injured bile ducts, and into epithelioid granulomata in PBC. The data further implicate bacterial materials derived from bile in the overall pathogenesis of PBC.

AB - The monocyte chemotactic proteins (MCPs) form a distinct structurally related subclass of C-C chemokines. MCPs select specific target cells due to binding to a distinct set of chemokine receptors and because of their effects on monocytes, and may participate in the process of granuloma formation during bacterial and/or mycobacterial infections. The aetiology of primary biliary cirrhosis (PBC) is still unclear, although bacterial infection and autoimmune processes have been implicated. In this study, the expression of three of the most potent monocyte chemoattractants, MCP-1, -2, and -3, was examined in patients with PBC and the data were compared with results for other liver diseases including primary sclerosing cholangitis (PSC), chronic viral hepatitis C, hepatic sarcoidosis, and normal liver. MCP-1 was expressed mainly in biliary epithelial cells of all liver specimens, irrespective of the cause of disease. Some mononuclear leukocytes in the portal tract expressed MCP-1 in all the disease groups examined and there were no significant differences in frequency between these groups. In contrast, more than 80% of PBC livers showed MCP-2- and MCP-3-positive mononuclear leukocyte infiltration in portal tracts, particularly around the bile ducts, whereas such cells were far less frequent in the other disease groups or in normal livers. Epithelioid granulomata of PBC patients contained MCP-2- and MCP-3-positive cells at their edge. In double staining experiments, more than 60% of the MCP-positive mononuclear cells co-expressed CD68, suggesting that a proportion of MCP-2- and MCP-3-positive cells are derived from monocytes. These monocytes expressing MCP-2 and MCP-3 may be responsible for the chemotactic activity of more monocytes. Such an expression pattern of MCP-1, -2 and -3 in portal tracts seems to be distinctive for PBC. This pattern underlines the importance of MCP-1, -2, and -3 in the recruitment of monocytes and possibly T lymphocytes into portal tracts, around the injured bile ducts, and into epithelioid granulomata in PBC. The data further implicate bacterial materials derived from bile in the overall pathogenesis of PBC.

KW - Chemokine

KW - Infection

KW - MCP-1

KW - MCP-2

KW - MCP-3

KW - Primary biliary cirrhosis

UR - http://www.scopus.com/inward/record.url?scp=0035168848&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035168848&partnerID=8YFLogxK

U2 - 10.1002/1096-9896(2000)9999:9999<::AID-PATH725>3.0.CO;2-P

DO - 10.1002/1096-9896(2000)9999:9999<::AID-PATH725>3.0.CO;2-P

M3 - Article

C2 - 11169522

AN - SCOPUS:0035168848

VL - 193

SP - 102

EP - 109

JO - Journal of Pathology

JF - Journal of Pathology

SN - 0022-3417

IS - 1

ER -