on March 22, 2012
During tissue damage, the protein of the alarmin family, HMGB1, released from the cells, was shown to be capable of attracting cells from the peripheral blood and to start the inflammatory process which can be either positive i.e., repair the damage or negative i.e., continue in a chronic inflammation. The mechanism by which HMGB1 induces cell migration was however unknown.
In this report recently published in J. Exp. Med, the group of Dr. Mariagrazia Uguccioni has discovered that at the base of the action of HMGB1 there is the formation of a complex with a chemokine, CXCL12. This complex acts through a receptor, CXCR4, on circulating cells and attracts the inflammatory cells on the site of damage.
Blocking the complex formation between HMGB1 and CXCL12 can be of benefit in the early stages of tissue damage (ischemia and trauma) as well as in chronic diseases such as in Rheumatoid Arthritis, situations in which the recruitment of inflammatory cells is mediated by HMGB1.
The work also shows the molecular structure of the complex, thus hoping to find drugs that would prevent the formation of this complex and block the migration of the inflammatory cells without inhibiting the other important functions of the alarmin.
The work was done in collaboration with other European institutes (San Raffaele Hospital in Milan, Center of Biotechnology in Madrid, MerckSerono in Geneva). It was driven by the group of Dr. Mariagrazia Uguccioni and was mostly done by Dr. Milena Schiraldi. Were also participating the IRB groups of Dr. Luca Varani and Prof. Marcus Thelen.
The research was supported by grants from the European Union, the SNF, and other national and international grants.
