Burying Dead Cells Requires Oxidative Signaling

The research here considers how the debris of dead cells is cleared away, something that has to happen efficiently in order to avoid inflammation and other issues in tissue. As is true of a range of beneficial processes in the body, this turns out to require a certain level of oxidative signaling. This is probably one of the reasons why long-term general use of antioxidants appears to be, on balance, modestly harmful to health and longevity. The process is interesting when considered in the context of recent work on necroptosis, a fairly recently discovered form of programmed cell death that results in inflammatory cell debris, as well as past considerations of cellular debris as a mechanism by which excess fat tissue produces chronic inflammation. Is this sort of thing important in the progression of aging, more of a root cause of many issues rather than a downstream consequence of failing maintenance processes? That is an interesting question.

Billions of cells die daily as a consequence of regular wear and tear, tissue turnover and during an inflammatory response. The body dedicates a significant amount of energy in the specific recognition and uptake of these dead cells via specific pathways. If you don't bury the dead cells, they can burst open and cause harm, however the underlying mechanisms are incompletely characterized. Now, researchers have uncovered how NADPH-oxidase is activated to generate reactive oxygen species (ROS) in macrophages, a kind of white blood cell that eats dead cells. These cells also are involved in getting rid of viruses and bacteria.

The presence of ROS is critical as its generation drives additional mechanisms involved in the digestion of cellular corpses to perform at an optimal level. This allows the macrophage to complete the digestion process of efferocytosis. "Independent of their role in microbial killing, we are gaining even greater appreciation of ROS for their huge role in the regulation of host immune response. Uncovering this role of ROS in the clearance of dead cells sheds some mechanistic insights on how oxidants function in limiting of host inflammation rather than activating it. When our bodies produce too much or too little ROS, we become pre-disposed to autoimmune disease and chronic inflammation. Producing just enough - the optimal level - is what's needed."

Link: http://uoflnews.com/post/uofltoday/uofl-research-proper-burial-of-dead-cells-limits-inflammation/


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