Key Protein Discovered To Be Critical Enabler For Cell Clearance

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Main Category: Biology / Biochemistry
Article Date: 08 Sep 2011 - 8:00 PDT

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A new UVA Health System study published online August 21, 2011 in the journal Nature reports that researchers have uncovered a critical enabler that allows phagocytic cells (cells that clean the body's dead cells) to continually and vigorously clean out our bodies of dead cells. The findings could contribute to a greater understanding of atherosclerosis and benefit many metabolic diseases, such as diabetes and obesity.

The healthy human body is highly efficient in cleaning itself. Every day our bodies shed between 100-200 billion dead or dying cells in a process called cell clearance. Phagocytes, professional cleaning cells, are responsible for 'cleaning' the body of dead, or 'apoptotic,' cells. Cell clearance is fundamental for maintaining a healthy physiological balance and preventing a number of chronic diseases.

Kodi Ravichandran, PhD, lead investigator of the new UVA Health System study explains:


"This process of cell clearance, in which a phagocyte consumes a dying cell, is akin to you having a neighbor move into your house with all his possessions. The phagocyte would need to sort and dispose of the excess material, while maintaining its normal form and function. Yet remarkably, we have far fewer phagocytes than dying cells in the body, which means each phagocyte would have to accommodate several neighbors." 



So far researchers have not been able to understand phagocytic cells' ability to continually consume dead cells, but UVA researchers have now uncovered a critical enabler that allows the phagocytic cell clearance. 



 The researchers discovered that the phagocyte Uncoupling Protein 2 (Ucp2) plays a vital part in regulating the appetite of the phagocyte. Ucp2 is generally located within the mitochondria, which is a key energy organelle within all cells. The researchers established that Ucp2 protein levels within the phagocytes increase when phagocytes start to eat their dying neighbors and as a result, the higher Ucp2 modifies membrane potential within the phagocyte mitochondria and increases the ability of a phagocyte to ingest multiple dead cells.



 Ravichandran who is chair of the UVA Department of Microbiology and director of the Center for Cell Clearance explains:

"Defining the factors that control the capacity of phagocytes to engulf apoptotic cells is important across a number of disciplines. The failure to promptly recognize and clear these dying cells has deleterious consequences to the body, predisposing it to autoimmunity, inflammation and atherosclerosis."



By heightening the appetite of phagocytes through the upregulation, or increase of Ucp2, researchers may be able to develop possible treatment strategies for a wide variety of diseases in which impaired clearance of dying cells often is seen.



 Study findings could also help in gaining a better understanding of atherosclerosis, a process involving continual thickening of plaque along artery walls. Earlier research revealed that cell clearance failure to clear out apoptotic cells (dead cells) contributes to atherosclerosis and that the loss of Ucp2 has also been associated with atherosclerosis. 



 Ravichandran concludes:

"Therefore, the connection between Ucp2 and cell clearance may help us identify new modes of treatment for atherosclerosis."

Understanding individual cell mechanisms in terms of managing energy metabolism is important for many metabolic diseases, such as diabetes and obesity, which affect over 600 million people worldwide. Identifying the process of how a phagocyte copes with the excess metabolic load while consuming dead cells would assist researchers to better understand and potentially alleviate metabolic diseases in the future. 


Ravichandran continues:

"Our next steps are targeted toward uncovering how we can naturally enhance the levels or activity of the Ucp2 protein and in turn modulate the energy metabolism."

Written by Petra Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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