A novel chemokine, Leukotactin-1, induces chemotaxis, pro-atherogenic cytokines, and tissue factor expression in atherosclerosis

Atherosclerosis. 2002 Apr;161(2):255-60. doi: 10.1016/s0021-9150(01)00634-7.

Abstract

Chemokines such as monocyte chemoattractant protein (MCP) -1 and interleukin (IL)-8 are known to be involved in various processes in atherosclerosis such as plaque formation, plaque rupture, and thrombus formation. We investigated whether a new chemokine, Leukotactin (LKN)-1, is involved in atherosclerosis. We tested the expression of LKN-1 by immunohistochemical methods in carotid atherosclerotic plaque specimen. Induction of pro-inflammatory cytokines, transmigration, and tissue factor (TF) expression were tested in THP-1 cells and human peripheral blood monocytes treated with recombinant human LKN-1. Immunohistochemical analyses revealed that expression of LKN-1 occurs in regions of plaques rich in foam cells. In a Boyden chamber assay, THP-1 cells treated with 0.01--10 nM of LKN-1 transmigrated through gelatin coated filters in a dose dependent manner. LKN-1 also induced the transient expression of TNF-alpha, IL-8, and MCP-1 within 15 min of the treatment of the THP-1 cells. When peripheral blood monocytes were treated with LKN-1, expression levels of TF and TF-mediated procoagulating activity were induced in a time- and dose-dependent manner. These results raise the possibility that LKN-1 is another chemokine that is involved in the atherogenesis. LKN-1 may chemoattract immune cells into the plaque, induce pro-inflammatory cytokines, and produce thrombi by inducing TF expression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carotid Artery Diseases / pathology*
  • Cells, Cultured
  • Chemokine CCL2 / metabolism*
  • Chemokines, CC / pharmacology*
  • Chemotaxis / drug effects
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Interleukin-8 / metabolism
  • Lymphocyte Activation / drug effects
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Sensitivity and Specificity
  • Thromboplastin / drug effects*
  • Thromboplastin / metabolism*

Substances

  • Chemokine CCL2
  • Chemokines, CC
  • Interleukin-8
  • Thromboplastin