Potential drug to treat sepsis
doi:10.1038/nindia.2018.63 Published online 22 May 2018
Researchers have identified a new immunomodulatory function of the adhesion protein fibulin-7 (Fbln7) that may help treat sepsis or blood infection and other inflammatory diseases caused by abnormal functions of immune cells1. The researchers from Indian Institute of Technology (IIT) in Roorkee and the National Institutes of Health, USA have filed a US patent for the above use.
The immune system consists of a variety of white blood cells (WBCs) or leukocytes. In response to any inflammatory and infectious stimulus, they respond by migrating to the affected site. While traveling through the tissue spaces, the activated WBCs interact with and bind to extracellular matrix proteins – for instance, collagen or fibronectin – via their surface receptor molecules called integrins thereby modulating various functions of the immune cells. During sepsis, there is abnormal activation and localization of important immune cells leading to their deposition in organs like lung, kidney and liver causing multi-organ failure and death.
Fbln7 has been identified as the latest member of the Fibulin family – a group of glycoproteins associated with membranes lining tissues and blood vessels and other matrices – but its functional significance was not known. In their study, using an animal model of sepsis, the researchers showed that Fbln7 – and its C-terminal fragment – could "inhibit adhesion, migration and production of inflammatory molecules" from immune cells suggesting that they could have therapeutic potential for treating immuno-pathological conditions like sepsis which require negative regulation of immune cell functions, the report says.
1. Sarangi, P. P. et al. Cell adhesion protein fibulin-7 and its C-terminal fragment negatively regulate monocyte and macrophage migration and functions in vitro and in vivo. FASEB. J. (2018) doi: 10.1096/fj.201700686RRR