Oxidation Found to Have Role in Cell-Death Alerts
Reactive oxygen species in apoptosis prevent signal from stimulating immune system
THURSDAY, July 24 (HealthDay News) -- The different immune system responses following necrosis or apoptosis of cells is influenced by high-mobility group box-1 protein (HMGB1) that may be released by the dying cells, as well as by reactive oxygen species (ROS), according to research published in the July 18 issue of Immunity.
Hirotaka Kazama, of the Washington University School of Medicine in St. Louis, and colleagues write that necrotic cells release HMGB1 upon dying, but apoptotic cells reportedly do not, although this theory has recently been questioned.
The authors report that activation of caspase -- which are enzymes that orchestrate apoptosis, with roles such as DNA fragmentation and membrane blebbing -- spurs mitochondria to create reactive oxygen species (ROS), which oxidize HMGB1 and prevent it from stimulating the immune system. When the researchers suppressed the ROS activity, apoptotic cells stimulated immune responses by scavenging or mutating a mitochondrial caspase target protein.
"We have found that cells undergoing apoptosis can release substantial levels of HMGB1; however, only HMGB1 released from apoptotic cells that do not make significant ROS is functional in stimulating immune responses. This suggests that a mechanism is in place to control the potential danger that released HMGB1 could pose if it leaked from apoptotic cells. Consequently, we would propose that it is not an inability to release a danger signal that determines whether a cell is tolerogenic but rather that the ability of the cell to generate oxidative conditions that can destroy danger signals is paramount," the authors write.