Different cytotoxic response to gadolinium between mouse and rat alveolar macrophages

Abstract

The cytotoxicity of gadolinium (Gd) chloride was investigated in alveolar macrophages (AM) cultured in vitro. A marked difference in the cytotoxic response to Gd was found between mouse and rat AM. The viability of rat AM was decreased by exposure to Gd at doses more than 3 μ m, while mouse AM appeared to be resistant even up to 1000 μ m Gd exposure. The decrease in the viability of rat AM exposed to Gd at doses up to 1000 μ m was mitigated by centrifugation and filtration of the culture medium containing Gd, or by the treatment of AM with lysosomotropic agents such as NH 4Cl or chloroquine, suggesting that the cytotoxic response of rat AM to Gd at doses up to 1000 μ m was dependent on the intracellular uptake and subsequent dissolution of Gd present in the culture medium in colloidal form. The phagocytic activity of mouse AM, evaluated by the uptake of latex particles, was higher than that of rat AM. Furthermore, quantitative analysis of Gd with inductively coupled plasma-mass spectrometry revealed that mouse AM took up a larger amount of Gd than rat AM. Therefore, the marked difference in the cytotoxic response to Gd between mouse and rat AM could not be attributed to the phagocytic activities for the colloidal form of Gd. The cytotoxic sensitivity of AM to Gd present in non-colloidal form was almost the same between mouse and rat AM. Therefore, it is suggested that the extent to which Gd-colloid phagocytosed is dissolved in the phago-lysosome or the subsequent process to exhibit the cytotoxicity may be different between mouse and rat AM.