Detection of monocyte chemoattractant protein-1 in human atherosclerotic lesions by an anti-monocyte chemoattractant protein-1 monoclonal antibody

Motohiro Takeya, Teizo Yoshimura, Edward J. Leonard, Kiyoshi Takahashi

Research output: Contribution to journalArticle

238 Citations (Scopus)

Abstract

The infiltration of blood monocytes into the subendothelial space is thought to be one of the most important pathologic events in early atherogenesis. To examine the mechanism of monocyte migration in early atherosclerotic lesions we investigated immunohistochemically the production of monocyte chemoattractant protein-1 (MCP-1) in various atherosclerotic lesions, including diffuse intimal thickening, fatty streaks, and atheromatous plaques, obtained during autopsies of patients of various ages. A highly specific anti-MCP-1 monoclonal antibody that does not cross-react with neutrophil-activating, attractant protein-1/interleukin-8 or platelet proteins that have an amino acid sequence similar to MCP-1 was used to localize MCP-1 in situ. To characterize the cells constituting the atherosclerotic lesions a panel of monoclonal and polyclonal antibodies that are specific to smooth muscle cells (HHF-35), monocyte/macrophages (HAM56, Leu-M3, Leu-M5, EBM11, and PM-2K), and endothelial cells (anti-von Willebrand factor) was used. Double immunohistochemical staining with anti-MCP-1 and one of the cell type-specific antibodies was performed to identify the nature of MCP-1-positive cells. Endothelial cells stained positively for MCP-1 in nine of 14 diffuse intimal thickening lesions. Scattered macrophages in thickened intima also were positive for MCP-1. Endothelial staining of MCP-1 was observed in 14 of 21 fatty streak lesions. Subendothelial macrophages were strongly stained for MCP-1 in all fatty streak lesions examined. Subendothelial macrophages were stained for MCP-1 in atherosclerotic plaques; however, endothelial cells were only slightly positive for MCP-1. A few smooth muscle cells in the intima were positive for MCP-1 in atheromatous plaques. From these results it is concluded that the cell populations positive for MCP-1 are different in early and advanced atherosclerotic lesions, and that the endothelial cells and subendothelial macrophages are considered to be the major sources of MCP-1 in early atherosclerotic lesions.

Original languageEnglish
Pages (from-to)534-539
Number of pages6
JournalHuman Pathology
Volume24
Issue number5
DOIs
Publication statusPublished - May 1993

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Keywords

  • anti-monocyte chemoattractant protein-1
  • atherosclerosis
  • double immunohistochemical staining
  • monoclonal antibody
  • monocyte chemoattractant protein-1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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