4-HYDROXYNONENAL-INDUCED CELL-DEATH IN MURINE ALVEOLAR MACROPHAGES

Oxidative stress is known to cause apoptosis in many cell types, yet t he mechanism of oxidative stress-induced apoptosis is not clear. Oxida tive stress has been described to cause peroxidation of polyunsaturate d fatty acids. 4-Hydroxynonenal (HNE) is a diffusible product of lipid peroxidation and has been shown to be toxic to cells. In this study, the effects of HNE on isolated alveolar macrophages (AIM) from two mur ine strains (C3H/HeJ and C57BL/6J) were examined. HNE induced the form ation of protein adducts in AMs from both strains of mice in a dose-de pendent manner, and the amounts of HNE-protein adducts formed in cells from both strains were very similar. In the HNE dose range from 1 to 100 mu M, AMs from both strains had very little necrosis as shown by t rypan blue staining. However, AMs from both C3H/HeJ and C57BL/6J mice had extensive apoptosis at 100 mu M HNE, but little or no apoptosis at 25 mu M HNE. Furthermore, AMs from C57BL/6J mice had significant apop tosis at 50 mu M HNE while AMs from C3H/HeJ mice had no significant ap optosis at this dose. At low doses of HNE (10 to 25 mu M), there was i nduction of heme oxygenase 1. The data indicated that HNE induces apop tosis in murine macrophages, and cells from different strains of mice have different sensitivities to the HNE-induced apoptosis. The cause o f the difference in susceptibility is not known, but it is possible th at different stress response and/or apoptosis-regulating proteins may be in part responsible. Our observation that a product of lipid peroxi dation causes apoptosis suggested that it might be a mediator for oxid ative stress-induced apoptosis. (C) 1996 Academic Press, Inc.