Sunday, May 5, 2013

Metal Ions Activate Vascular Endothelial Cells and Increase Lymphocyte Chemotaxis and Binding.

2013 Apr 29. doi: 10.1002/jor.22377. [Epub ahead of print]



Department of Orthopaedic Surgery, Medical College of Wisconsin, PO Box 26099, West Wisconsin Avenue, Milwaukee, Wisconsin, 53226.


Metal on metal articulations in hip arthroplasty offer advantages, including lower volumetric wear compared to conventional metalonpolyethylene bearings, and increased resistance to dislocation. Reports described early failures, with histologic features similar to a Type IV immune response. Mechanisms by which metal wear products cause this reaction are not completely understood. We hypothesized a mechanism through direct activation of endothelial cells (ECs) by metal ions, resulting in both vasculitis and accumulation of lymphocytes without prior immune sensitization. Effects of metal ions were evaluated using human ECs in culture. Alterations in chemotactic proteins IL8 and MCP1 were assessed, as was upregulation of the adhesion molecule ICAM-1 and lymphocyte binding to ECs. Cobalt increased secretion of IL8 and MCP1 significantly, and upregulated the expression of ICAM-1 in ECs compared to stimulation by chromium and controls. Binding of lymphocytes to ECs and transEC migration were both significantly increased by cobalt but not chromium. These findings suggest that cobalt contributes more to the activation of ECs and lymphocyte binding than chromium without an allergic response. Some of the adverse tissue reactions to implants with components made of cobalt-chromium-molybdenium alloys may be due in part to activation of the endothelium by metal ions. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res


What are vascular endothelial cells?

Vascular endothelial growth factor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate. Serum concentration of VEGF is high in bronchial asthma and low in diabetes mellitus. VEGF's normal function is to create new blood vessels during embryonic development, new blood vessels after injury, muscle following exercise, and new vessels (collateral circulation) to bypass blocked vessels.

When VEGF is overexpressed, it can contribute to disease. Solid cancers cannot grow beyond a limited size without an adequate blood supply; cancers that can express VEGF are able to grow and metastasize. Overexpression of VEGF can cause vascular disease in the retina of the eye and other parts of the body. Drugs such as bevacizumab can inhibit VEGF and control or slow those diseases.

Why is this study interesting?

I had a conversation recently with a biochemist who suggested that cobalt not chromium might be the key component for studying cancer related issues surrounding the hip.  Thought this was quite an interesting study.   In my situation, I have stage 4 renal cell carcinoma.  A major component of that disease state is VEGF.  Kidney cancer is a very vascular disease.

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