Exploiting the anti-inflammatory function of macrophages offers considerable potential for the treatment of diseases

Researchers at the University of Illinois at Chicago have identified a molecular switch that allows immune cells called macrophages to clean up cell debris caused by infections instead of contributing to inflammation and lesions tissue. Their results are reported in the newspaper Proceedings of the National Academy of Sciences.

Macrophages are a type of immune cell found throughout the body. These cells can produce moderate inflammation because the inflammatory signals bring other immune cells to a specific place to eliminate an infection. However, when inflammation becomes uncontrollable, as is the case with inflammatory diseases, it can cause excessive damage to cells and tissues, contributing to a vicious cycle that is very difficult to remove. But macrophages also play an important role in reducing inflammation when they engulf cellular debris or foreign microbes that contribute to inflammation. The mechanism at the origin of the ability of macrophages to switch between these two diametrically opposed roles has long puzzled scientists.

Researchers led by Saroj Nepal, a research badistant in the pharmacology department of the UIC's Faculty of Medicine, discovered that a molecule called Gas6 was needed to induce macrophages to play their anti-inflammatory role in engulfing and digesting cellular debris that may contribute to inflammation. The molecule could serve as a potential drug target for drug manufacturers interested in convincing cells to reach their anti-inflammatory state to help treat people.

Nepal and colleagues found in a murine model of acute lung injury that pulmonary macrophages express both inflammatory and anti-inflammatory proteins. One of the anti-inflammatory proteins was Gas6. In a murine model of acute lung injury in which animal macrophages were artificially cleared of Gas6, the clearance of inflammatory molecules and proteins in the lungs was severely impaired and inflammation could not be resolved. When they artificially increased Gas6 levels in mouse macrophages, inflammation was resolved much faster than in mice with normal macrophages.

Exploiting the anti-inflammatory function of macrophages using the Gas6 switch offers considerable potential for the treatment of diseases ranging from heart disease to cancer, to rheumatoid arthritis, where inflammation is an essential underlying characteristic. "

Saroj Nepal, Research Assistant Professor, Department of Pharmacology, UIC College of Medicine