Abstract | BACKGROUND: METHODS AND RESULTS: Fibrous and atheromatous plaques but not normal arteries contained NE. In particular, NE abounded in the macrophage-rich shoulders of atheromatous plaques with histological features of vulnerability. Neutrophil elastase and macrophages colocalized in such vulnerable plaques (n=7). In situ hybridization revealed NE mRNA in macrophage-rich areas, indicating local production of this enzyme. Freshly isolated blood monocytes, monocyte-derived macrophages, and vascular endothelial cells in culture produced active NE and contained NE mRNA. Monocytes produced NE constitutively, with little regulation by cytokines IL-1beta, TNF-alpha, or IFN-gamma but released it when stimulated by CD40 ligand, a cytokine found in atheroma. CONCLUSIONS: These findings point to a novel role for the serine protease, neutrophil elastase, in matrix breakdown by macrophages, a critical process in adaptive remodeling of vessels and in the pathogenesis of arterial diseases.
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Authors | Clare M Dollery, Caroline A Owen, Galina K Sukhova, Alexandra Krettek, Steven D Shapiro, Peter Libby |
Journal | Circulation
(Circulation)
Vol. 107
Issue 22
Pg. 2829-36
(Jun 10 2003)
ISSN: 1524-4539 [Electronic] United States |
PMID | 12771009
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antigens, CD
- Antigens, Differentiation, Myelomonocytic
- CD68 antigen, human
- Cytokines
- RNA, Messenger
- CD40 Ligand
- Leukocyte Elastase
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Topics |
- Antigens, CD
(biosynthesis)
- Antigens, Differentiation, Myelomonocytic
(biosynthesis)
- Arteriosclerosis
(enzymology, pathology)
- Blotting, Western
- CD40 Ligand
(metabolism, pharmacology)
- Carotid Arteries
(pathology)
- Cell Differentiation
- Cells, Cultured
- Cytokines
(pharmacology)
- Disease Progression
- Endothelium, Vascular
(cytology, metabolism)
- Humans
- Immunohistochemistry
- In Situ Hybridization
- Leukocyte Elastase
(biosynthesis, genetics)
- Macrophages
(enzymology, pathology)
- Monocytes
(cytology, drug effects, enzymology)
- Muscle, Smooth, Vascular
(cytology, metabolism)
- RNA, Messenger
(biosynthesis)
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