Prof. Dr.
Jürgen Metz

Prof. Dr. Jürgen Metz

MD 1968 University of Heidelberg, Germany

Postdoctoral work at Departments of Surgery, Internal Medicine, Sport Medicine, Physiology, and Anatomy and Cell Biology, University of Heidelberg 1969-1977

Specialization in Sport Medicine 1974; Laboratory Medicine 1977

Professor of Anatomy and Cell Biology, University of Heidelberg since 1977

Activation and Inflammatory Response of Mononuclear Cells

Current Research

Inflammatory processes contribute to the pathogenesis of diseases like arteriosclerosis or Alzheimer disease. To characterize the activation and inflammatory response of mononuclear cells, their phenotype is studied in humans and experimental animals. In further studies, the inflammatory response as well as the efficacy and mode of action of anti-inflammatory substances are investigated in vitro in human monocytes and macrophages.

Inflammatory processes in mononuclear cells of the atherosclerotic plaque

Morphometric analyses of the plaque size and cellularity by use of a computerized image analysis system developed in our group reveal that a significant decrease of inflammatory plaque mononuc-lear cells, which is the key event of plaque stabilization, occurs after long-term normalization of former increased lipid levels. The number and phenotype of the mononuclear cells within the arterial intima reflect an inflammatory response to numerous stimuli, which in clinics are rated as risk factors. Cellular details of the inflammatory process within mononuclear cells are visualized by use of immunohistochemical markers, such as LN3, CR3/43 (MHC II antigens), MnSOD (antioxidant scavenger enzyme), Cox2 (cyclooxygenase 2), TNF? (tumor necrosis factor), p53 (oncosuppressor protein), TUNEL (apoptosis), MIF (macrophage migration inhibitory factor), MIC-1/GDF-15 (growth/differentiation factor-15). Subpopulations of plaque mononuclear cells showed increased oxidative stress and eicosanoid metabolism, up regulation of inflammatory cytokines and MHC II antigens, cytotoxic damages, and up regulation of MIF and Mic-1.

Inflammatory mediators in human monocytes and macrophages

Molecular details of the inflammatory signal transduction pathway are studied in human mononuclear cells, which are isolated from healthy blood donors and patients with risk factors of coronary heart disease. Exposition of mononuclear cells to oxidized lipoproteins supports the results of those within the arteriosclerotic plaques on the protein and gene level.

Pro- and anti-inflammatory effects of numerous substances are tested in human monocytes by use of quantitative apoptosis tests, nitrite, TNF?, and COX2 measurements. Cytotoxicity of numerous substances is tested in human macrophages by use of quantitative apoptosis tests, and dye exclusion tests (necrosis).

Future Projects and Goals

Our long-term goal is to understand the contribution of pro- and anti-inflammatory processes to the regulation of survival and cell death of mononuclear cells. We are searching for markers in peripheral blood mononuclear cells, which are predictive of chronic inflammatory processes in the vessel wall as well as other organs and allow the development of new specific therapeutic strategies.

Selected publications

(1) Kinscherf R, Claus R, Wagner M, Gehrke C, Kamencic H, Hou D, Chen M, Nauen O, Schmiedt W, Kovacs G, Pill J, Metz J, Deigner HP (1998) Apoptosis caused by Oxidized-LDL is manganese superoxide dismutase and p53-dependent. FASEB J 12: 461- 467

(2) Schmiedt W, Kinscherf R, Deigner HP, Kamencic H, Nauen O, Kilo J, Oelert H, Metz J, Bhakdi S (1998) Complement C6-deficiency protects against diet-induced atherosclerosis in rabbits. Arterioscler Thromb Vasc Biol 18: 1790-1795.

(3) Hehrlein C; Kaiser S; Riessen R; Metz J; Fritz P; Kübler W (1999) External beam radiation after stent implantation increases neointimal hyperplasia by augmenting smooth muscle cell proliferation and extracellular matrix accumulation. J. American College Cardiology 34(2) 561-566

(4) Kinscherf R; Wagner M; Kamencic H; Bonaterra CA; Hou DM; Schiele RA; Deigner HP; Metz J (1999) Characterization of apoptotic macrophages in atheromatous tissue of humans and heritable hyperlipidemic rabbits Atherosclerosis 144 (1): 33-39

(5) Deigner HP, Claus R, Bonaterra GA, Gehrke C, Bibak N, Blaess M, Cantz M, Metz J Kinscherf R (2001) Ceramide induces aSMase expression: Implications for oxLDL-induced apoptosis. FASEB 15(3): 807-14

Letzte Änderung: Tue, 13.09.2016
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