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ARE MACROPHAGES ACTIVATED AND INDUCE PULMONARY INJURY BY INTRACELLULARLY BIOAVAILABLE IRON?
Citation:
Kreyling, W., M. Schladweiler, S E. Becker, D L. Costa, P. Mayer, A. Ziesenis, AND U P. Kodavanti. ARE MACROPHAGES ACTIVATED AND INDUCE PULMONARY INJURY BY INTRACELLULARLY BIOAVAILABLE IRON? Presented at American Thoracic Society, Atlanta, GA, May 17-22, 2002.
Description:
ARE MACROPHAGES ACTIVATED AND INDUCE PULMONARY INJURY BY INTRACELLULARLY BIOAVAILABLE IRON? UP Kodavanti1, MCJ Schladweiler1, S Becker2, DL Costa1, P Mayer3, A Ziesenis3, WG Kreyling3, 1ETD, 2HSDivision, NHEERL, USEPA, Research Triangle Park, NC, USA, and 3GSF, Inhalation Biology, Neuherberg/Munich, Germany.
Iron (Fe) is ubiquitous present in ambient PM air pollution; however, its role in pulmonary injury has not been fully examined. Objectives of this study were: 1) if there is bioavailable iron inside alveolar macrophages (AM), will AM be protective or will inflammatory reactions be initiated? 2) To understand how genetic susceptibility to cardiovascular disease may render an animal model more vulnerable to Fe particle-induced lung injury. Monodisperse porous Fe2O3 particles were synthesized and tested to partly dissolve intracellularly in cultured AM (1% of Fe mass in 24 hours) but not extracellularly. Wistar-Kyoto (WKY) and Spontaneously Hypertensive (SH) rats were intratracheally (IT) instilled with 0, 1.3, or 4.0 mg/kg Fe2O3 particles, suspended in saline, and indices of pulmonary injury determined 24 or 96 h later. Fe2O3 particles were clearly phagocytiz ed in AM. Only slight neutrophilic inflammation was evident in the high dose particle-exposed rats. SH rats mounted a slightly greater response than WKY rats. Other indices of pulmonary injury, such as protein leakage also indicated a small but significant increase with high dose exposure in SH rats. The activation of AM, phagocytosis, and IL-6 release were not affected by Fe2O3 particles in vitro. was concluded that iron released intracellularly from Fe2O3 particles and retained in AM is not very inflammatory in vivo in both normal and susceptible rats when compared to residual oil fly ashes where iron is extracellularly bioavailable. (This abstract does not necessarily reflect US EPA policy).