Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes

Am J Pathol. 2001 Mar;158(3):879-91. doi: 10.1016/S0002-9440(10)64036-9.


Inflammation and oxidative stress contribute to the pathogenesis of many human diseases including atherosclerosis. Advanced human atheroma contains high levels of the enzyme myeloperoxidase that produces the pro-oxidant species, hypochlorous acid (HOCl). This study documents increased numbers of myeloperoxidase-expressing macrophages in eroded or ruptured plaques causing acute coronary syndromes. In contrast, macrophages in human fatty streaks contain little or no myeloperoxidase. Granulocyte macrophage colony-stimulating factor, but not macrophage colony-stimulating factor, selectively regulates the ability of macrophages to express myeloperoxidase and produce HOCl in vitro. Moreover, myeloperoxidase-positive macrophages in plaques co-localized with granulocyte macrophage colony-stimulating factor. Pro-inflammatory stimuli known to be present in human atherosclerotic plaque, including CD40 ligand, lysophosphatidylcholine, or cholesterol crystals, could induce release of myeloperoxidase from HOCl production by macrophages in vitro. HOCl-modified proteins accumulated at ruptured or eroded sites of human coronary atheroma. These results identify granulocyte macrophage colony-stimulating factor as an endogenous regulator of macrophage myeloperoxidase expression in human atherosclerosis and support a particular role for the myeloperoxidase-expressing macrophages in atheroma complication and the acute coronary syndromes.

Publication types

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

MeSH terms

  • Arteriosclerosis / enzymology
  • Arteriosclerosis / etiology*
  • Arteriosclerosis / pathology
  • CD40 Antigens / pharmacology
  • Cell Differentiation
  • Cells, Cultured
  • Cholesterol / pharmacology
  • Gene Expression Regulation
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Humans
  • Hypochlorous Acid / metabolism
  • Lysophosphatidylcholines / pharmacology
  • Macrophages / drug effects
  • Macrophages / enzymology*
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / enzymology
  • Myocardial Infarction / enzymology
  • Myocardial Infarction / etiology*
  • Myocardial Infarction / pathology
  • Peroxidase / biosynthesis*
  • Phenotype
  • Reactive Oxygen Species / metabolism
  • Syndrome
  • Tunica Intima / enzymology


  • CD40 Antigens
  • Lysophosphatidylcholines
  • Reactive Oxygen Species
  • Hypochlorous Acid
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Cholesterol
  • Peroxidase