Effects of Alpha, Beta-Unsaturated Aldehydes on Macrophage and Neutrophil Membrane Function, Fluidity and Sulfhydryl Status
We have postulated that oxidative damage in the lung may be mediated by alpha,beta-unsaturated aldehydes formed during oxidant stress by ozone. As such, we are investigating the toxic effects of alpha,beta-unsaturated aldehydes on alveolar macrophages since these are key cells in the lung, important for the detoxification and removal of inhaled particles and for their interaction with lymphoid cells for immune functions. Since many of these functions are critically dependent on the integrity of the macrophage plasma membrane, we have concentrated our efforts on the effects of alpha,beta-unsaturated aldehydes on macrophage plasma membrane function and dynamic properties. The alpha,beta-unsaturated aldehydes inhibit the plasma membrane NADPH-dependent oxidase which metabolizes oxygen to superoxide anion radical, a precursor species to bactericidal active oxygen species such as •OH and H2O2. The observed IC50’s for inhibition of the macrophage oxidase are 24, 77 and 240 uM for acrolein, trans-4-hydroxynonenal and crotonaldehyde, respectively.1 Similar IC50’s were obtained for the inhibition by these aldehydes of the corresponding oxidase in human neutrophils.2
KeywordsAlveolar Macrophage Sulfhydryl Group Reactive Aldehyde Lipid Fluidity Superoxide Anion Radical Production
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