Induction of apoptosis in human microvascular endothelial cells by divalent cobalt ions. Evidence for integrin-mediated signaling via the cytoskeleton.
Wound healing following implantation is characterized by an acute inflammatory reaction and a subsequent reorganizing phase in which angiogenesis is involved. Endothelial cells (EC) participate in both inflammation and angiogenesis. Thus, the effects on functions of EC exerted by implanted materials could affect the progression of wound healing. The corrosion of metallic implants can cause high concentrations of heavy metal ions in the peri-implant tissues. The purpose of the present study was to test the effects of possible corrosion products on the function and viability of human EC in vitro. Long-term exposure of EC to CoCl2 and NiCl2 (3 days, 0.7 mM) leads to a decrease of cell number and changes in cellular morphology. However, the morphological changes between CoCl2- and NiCl2-treated cells differ significantly. The changed morphology of CoCl2-treated EC and the fragmented DNA pattern indicates apoptosis. Nickel-treated cells demonstrated necrosis. The activity of integrins was tested by an assay of cellular adhesion on collagen-coated surfaces. It was shown that the number of adherent cells significantly decreased upon exposure to CoCl2. Our studies suggest that induction of cell death in EC upon exposure to CoCl2 could be attributed to impaired integrin signaling, which leads to a damaged cytoskeleton and culminates in apoptosis.
Peters
K
K
Institute of Pathology, Johannes Gutenberg University, Langenbeckstr. 1, 55101 Mainz, Germany. peters@pathologie.klinik.uni-mainz.de
Unger
R E
RE
Barth
S
S
Gerdes
T
T
Kirkpatrick
C J
CJ