Proper Burial of Dead Cells Limits Inflammation

Dentistry Today

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Dead cells that accumulate in the body can contribute to inflammation and predispose people to multiple chronic inflammatory conditions such as rheumatoid arthritis, cardiovascular diseases, Crohn’s disease, or lupus by uncharacterized pathways, according to a multi-university team of researchers.

“Billions of cells die daily as a consequence of regular wear and tear, tissue turnover, and during and inflammatory response. The body dedicates a significant amount of energy in the specific recognition and uptake of these dead cells via specific pathways,” said Juhi Bagaitkar, PhD, a researcher in the University of Louisville School of Dentistry’s Department of Oral Immunology and Infectious Diseases.

“If you don’t bury the dead cells, they can burst open and cause harm, however the underlying mechanisms are incompletely characterized,” Bagaitkar said.

The researchers 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.

According to the researchers, 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 enables the microphage to complete the digestion process of efferocytosis, meaning to “bury the dead.”

“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,” Bagaitkar said. 

“When our bodies produce too much or too little ROS, we become predisposed to autoimmune disease and chronic inflammation,” Bagaitkar said. “Producing just enough, the optimal level, is what’s needed.”

The study, “NADPH oxidase inflammation regulates apoptotic neutrophil clearance by murine microphaes,” was published by blood.

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