Tissue-destructive macrophages in giant cell arteritis

Heike L. Rittner, Markus Kaiser, Alexander Brack, Luke I. Szweda, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Giant cell arteritis (GCA) is an inflammatory vasculopathy in which T cells and macrophages infiltrate the wall of medium and large arteries. Clinical consequences such as blindness and stroke are related to arterial occlusion. Formation of aortic aneurysms may result from necrosis of smooth muscle cells and fragmentation of elastic membranes. The molecular mechanisms of arterial wall injury in GCA are not understood. To identify mechanisms of arterial damage, gene expression in inflamed and unaffected temporal artery specimens was compared by differential display polymerase chain reaction. Genes differentially expressed in arterial lesions included 3 products encoded by the mitochondrial genome. Immunohistochemistry with antibodies specific for a 65-kDa mitochondrial antigen revealed that increased expression of mitochondrial products was characteristic of multinucleated giant cells and of CD68+ macrophages that cluster in the media and at the media-intima junction. 4-Hydroxy-2-nonenal adducts, products of lipid peroxidation, were detected on smooth muscle cells and on tissue infiltrating cells, in close proximity to multinucleated giant cells and CD68 + macrophages. Also, giant cells and macrophages with overexpression of mitochondrial products were able to synthesize metalloproteinase-2. Our data suggest that in the vascular lesions characteristic for GCA a subset of macrophages has the potential to support several pathways of arterial injury, including the release of reactive oxygen species and the production of metalloproteinase-2. This macrophage subset is topographically defined and is also identified by overexpression of mitochondrial genes. Because these macrophages have a high potential to promote several mechanisms of arterial wall damage, they should be therapeutically targeted to prevent blood vessel destruction.

Original languageEnglish (US)
Pages (from-to)1050-1058
Number of pages9
JournalCirculation Research
Volume84
Issue number9
DOIs
StatePublished - May 14 1999

Fingerprint

Giant Cell Arteritis
Macrophages
Giant Cells
Metalloproteases
Smooth Muscle Myocytes
Blood Vessels
Temporal Arteries
Mitochondrial Genome
Mitochondrial Genes
Aortic Aneurysm
Wounds and Injuries
Blindness
Lipid Peroxidation
Reactive Oxygen Species
Necrosis
Arteries
Immunohistochemistry
Stroke
T-Lymphocytes
Gene Expression

Keywords

  • Macrophage
  • Metalloproteinase
  • Reactive oxygen species
  • Vasculitis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Rittner, H. L., Kaiser, M., Brack, A., Szweda, L. I., Goronzy, J. J., & Weyand, C. M. (1999). Tissue-destructive macrophages in giant cell arteritis. Circulation Research, 84(9), 1050-1058. https://doi.org/10.1161/01.RES.84.9.1050

Tissue-destructive macrophages in giant cell arteritis. / Rittner, Heike L.; Kaiser, Markus; Brack, Alexander; Szweda, Luke I.; Goronzy, Jörg J.; Weyand, Cornelia M.

In: Circulation Research, Vol. 84, No. 9, 14.05.1999, p. 1050-1058.

Research output: Contribution to journalArticle

Rittner, HL, Kaiser, M, Brack, A, Szweda, LI, Goronzy, JJ & Weyand, CM 1999, 'Tissue-destructive macrophages in giant cell arteritis', Circulation Research, vol. 84, no. 9, pp. 1050-1058. https://doi.org/10.1161/01.RES.84.9.1050
Rittner HL, Kaiser M, Brack A, Szweda LI, Goronzy JJ, Weyand CM. Tissue-destructive macrophages in giant cell arteritis. Circulation Research. 1999 May 14;84(9):1050-1058. https://doi.org/10.1161/01.RES.84.9.1050
Rittner, Heike L. ; Kaiser, Markus ; Brack, Alexander ; Szweda, Luke I. ; Goronzy, Jörg J. ; Weyand, Cornelia M. / Tissue-destructive macrophages in giant cell arteritis. In: Circulation Research. 1999 ; Vol. 84, No. 9. pp. 1050-1058.
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