Abstract
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.
Keywords
MyeloperoxidaseMacrophageAtheromaInflammationGranulocyteImmunologyGranulocyte macrophage colony-stimulating factorFoam cellMedicineIn vitroBiologyInternal medicineCytokineBiochemistry
MeSH Terms
ArteriosclerosisCD40 AntigensCell DifferentiationCellsCulturedCholesterolGene Expression RegulationGranulocyte-Macrophage Colony-Stimulating FactorHumansHypochlorous AcidLysophosphatidylcholinesMacrophagesMonocytesMyocardial InfarctionPeroxidasePhenotypeReactive Oxygen SpeciesSyndromeTunica Intima
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Publication Info
- Year
- 2001
- Type
- article
- Volume
- 158
- Issue
- 3
- Pages
- 879-891
- Citations
- 697
- Access
- Closed
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Cite This
Seigo Sugiyama,
Yoshikatsu Okada,
Galina K. Sukhova
et al.
(2001).
Macrophage Myeloperoxidase Regulation by Granulocyte Macrophage Colony-Stimulating Factor in Human Atherosclerosis and Implications in Acute Coronary Syndromes.
American Journal Of Pathology
, 158
(3)
, 879-891.
https://doi.org/10.1016/s0002-9440(10)64036-9
Identifiers
- DOI
- 10.1016/s0002-9440(10)64036-9
- PMID
- 11238037
- PMCID
- PMC1850342