0000000000013712
AUTHOR
M Wagner
Current trends in biocompatibility testing
Biocompatibility remains the central theme for biomaterials applications in medicine. It is generally accepted that this term means not only absence of a cytotoxic effect but also positive effects in the sense of biofunctionality, i.e. promotion of biological processes which further the intended aim of the application of a biomaterial. The national and international standards for testing regimes represent a lowest common denominator for such applications and do not necessarily ensure that optimal function will be achieved. The authors' thesis is that biocompatibility testing has scope for extensive development with respect to biofunctionality. The present paper reviews current trends in the…
The role of metal corrosion in inflammatory processes: induction of adhesion molecules by heavy metal ions
Prosthetic devices undergo corrosion processes after implantation including the release of certain amounts of metal ions into the adjacent tissues. On reaching the bloodstream, a systemic influence of those ions may be envisaged. Cell adhesion molecules (CAMs) are recognized as an essential component of the mechanisms of endothelial damage. To study the influence of selected heavy metals on human umbilical vein endothelial cells (HUVEC) EIA methods were used to evaluate cellular expression of E-selectin, ICAM-1, VCAM-1 and GMP-140 under the influence of high (cytotoxic) very low (non-cytotoxic) concentrations of Zn, Ni, Co and Cr. The de novo synthesis of CAMs was studied with the help of m…
Comparative Studies on Vascular Endothelium in vitro
Recent studies have presented evidence that the processes of hypoxaemia and reperfusion are involved in several pathogenetic mechanisms of atherosclerotic lesions. The ability of hypoxaemia to activate circulating white blood cells (WBCs) and enhance WBC-endothelial cell (EC) interactions is suspected to be a major factor in deleterious processes in the blood vessel wall. Various groups have suggested that cell adhesion molecules (CAMs), such as ICAM-1, VCAM-1 and E-selectin and their leukocyte ligands are involved in intercellular activities of the relevant cell types. We studied the effects of different oxygen tensions, simulating normoxic conditions, hypoxia and hyperoxia in vitro with t…
Physiology and cell biology of the endothelium: a dynamic interface for cell communication.
This manuscript presents a brief overview of the physiology and cell biology of the endothelium, which is the basis for understanding the role of endothelial cells in pathological processes as diverse as atherosclerosis, tumour intravasation and multiple organ failure. Following consideration of general aspects of endothelial function in regulating haemostasis, vascular tone and growth, special emphasis will be placed on endothelial regulation of the inflammatory response, which centres on the microcirculation. A particular role in inflammation is played by cell adhesion molecules (CAM), expressed both on endothelial and blood cells. Cell and molecular biological methods to investigate the …
Comparative Studies on Vascular Endothelium in vitro
Endothelial cells (EC) are very responsive to proinflammatory cytokines, e.g. interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha), as well as to bacterial lipopolysaccharide. EC are stimulated by these substances to secrete chemotactic factors and to increase expression of cell adhesion molecules (CAM), leading to dramatically altered interactions with leukocytes, e.g. granulocytes and monocytes. In these interactions E-selectin, ICAM-1 and VCAM-1 are known to play an important role, as they are presented by the EC and interact with corresponding ligands on the white blood cell membranes. These adhesion molecules have been studied worldwide in a variety of in vitro experiments …
Induction of stress proteins in human endothelial cells by heavy metal ions and heat shock.
In the present study, we compared the induction of heat shock proteins (HSPs) by heat and heavy metal ions in three different endothelial cell types, namely, human umbilical vein endothelial cells, human pulmonary microvascular endothelial cells, and the cell line EA.hy 926. Our results show that especially Zn2+and Cd2+are inducers of 70-kDa (HSP70), 60-kDa (HSP60), 32-kDa (HSP32), and 27-kDa (HSP27) HSPs. The strength of inducibility is specific for each HSP. Ni2+and Co2+only show an inducible effect at very high concentrations, that is, in the clearly cytotoxic range. Furthermore, we investigated the time course of HSP expression and the involvement of heat shock factor-1. Our study demon…
Mechanisms of cell activation by heavy metal ions
Heavy metal ions can be released by corroding metallic implants into the surrounding tissue. When they enter blood vessels some of them are carried by proteins like albumin and can be taken up by endothelial cells lining the vessels. To study their involvement in the inflammatory response we investigated heavy metal ion induced effects in cultured human vascular endothelial cells (HUVECs). NiCl2 and CoCl2 upregulate, especially in concentrations of 1 mM, the expression of adhesion molecules (e.g., E-selectin and intercellular adhesion molecule-1), as well as the cytokines IL-6 and IL-8, as shown by enzyme immunoassay and Northern blot analysis. In addition, possible signal transduction mech…
Effects of Cytokines on the Expression of Cell Adhesion Molecules by Cultured Human Omental Mesothelial Cells
Cultured mesothelial cells (HOMES) are very responsive to the proinflammatory cytokines, interleukin (IL)-1 and tumor necrosis factor-alpha (TNF-alpha). E-selectin, ICAM-1 and VCAM-1 are known to play an important role, because they are presented by diverse cell types, for example endothelial cells (ECs), and interact with co-responding ligands on white blood cell membranes. In this study, the expression of ICAM-1, VCAM-1, E-selectin as well as PECAM-1 on cultured HOMES was studied over 5, 24, 48 and 72 h exposure to IL-1 beta, interferon-gamma and TNF-alpha. In previous studies we have shown that IL-1 beta and TNF-alpha increase the expression of ICAM-1, E-selectin and VCAM-1 on the cytopl…
Heavy metal ion induction of adhesion molecules and cytokines in human endothelial cells: the role of NF-kappaB, I kappaB-alpha and AP-1.
We analyzed the influence of heavy-metal ions on human umbilical vein endothelial cells (HUVEC) in comparison to proinflammatory cytokines (TNF-alpha, IL-1beta) and lipopolysaccharide (LPS). Adhesion molecule and cytokine expressions are upregulated by heavy-metal exposure. Expression of E-selectin on the cell surface was strongly induced by 1-mM concentrations of NiCl2 and CoCl2, whereas ZnCl2 and CrCl3 had no influence. Furthermore, it is shown that NiCl2 induces mRNA expression of E-selectin, intercellular adhesion molecule-1, IL-6 and IL-8 in a 1-mM concentration. The transcription factor NF-kappaB is known to be involved in the regulation of adhesion molecule expression in endothelial …
Focal adhesions and assessment of cytotoxicity
Focal adhesions are highly ordered assemblies of transmembrane receptors, extracellular matrix proteins, and a large number of cytoplasmic proteins, including structural proteins, as well as tyrosine kinases, phosphatases, and their substrates. They are now accepted as a prime component of signal transduction. Because focal adhesions also play an important role in cell morphology and migration, it can be argued that their presence is indicative of healthy cells. This has been the reason for several research groups to conclude that biomaterials sustaining focal adhesion assembly are biocompatible. In this study we demonstrate that cells under cytotoxic stress may still be able to retain thei…