Nadra, Imad and Boccaccini, Aldo R. and Philippidis, Pandelis and Whelan, Linda C. and McCarthy, Geraldine M. and Haskard, Dorian O. and Landis, R. Clive (2008) Effect of particle size on hydroxyapatite crystal-induced tumor necrosis factor alpha secretion by macrophages. ATHEROSCLEROSIS, 196 (1). pp. 98-105. ISSN 0021-9150
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Macrophages may promote a vicious cycle of inflammation and calcification in the vessel wall by ingesting neointimal calcific deposits (predominantly hydroxyapatite) and secreting tumor necrosis factor (TNF)alpha, itself a vascular calcifying agent. Here we have investigated whether particle size affects the proinflammatory potential of hydroxyapatite crystals in vitro and whether the nuclear factor (NF)-kappa B pathway plays a role in the macrophage TNF alpha response. The particle size and nano-topography of nine different crystal preparations was analyzed by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and gas sorbtion analysis. Macrophage TNF alpha secretion was inversely related to hydroxyapatite particle size (P = 0.011, Spearman rank correlation test) and surface pore size (P = 0.014). A necessary role for the NF-kappa B pathway was demonstrated by time-dependent I kappa B alpha degradation and sensitivity to inhibitors of I kappa B alpha degradation. To test whether smaller particles were intrinsically more bioactive, their mitogenic activity on fibroblast proliferation was examined. This showed close correlation between TNF alpha secretion and crystal-induced fibroblast proliferation (P = 0.007). In conclusion, the ability of hydroxyapatite crystals to stimulate macrophage TNF alpha secretion depends on NF-kappa B activation and is inversely related to particle and pore size, with crystals of 1-2 mu m diameter and pore size of 10-50 angstrom the most bioactive. Microscopic calcitic deposits in early stages of atherosclerosis may therefore pose a greater inflammatory risk to the plaque than macroscopically or radiologically visible deposits in more advanced lesions. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
|Uncontrolled Keywords:||atherosclerosis pathophysiology; calcification; macrophage; inflammation|
|Subjects:||Biomedical Science > Nanobiotechnology|
NanoSafety > Environment, health and safety aspects of nanotechnology
|Deposited By:||M T V|
|Deposited On:||15 Dec 2008 11:49|
|Last Modified:||15 Dec 2008 11:49|
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