Researchers from the Indian Institute of Technology (IIT) Roorkee have identified a new immunomodulatory function of a protein that could potentially help in treating sepsis and other inflammatory diseases caused by abnormal functions of immune cells.
"Abnormal functions of immune cells are associated with many pathological conditions such as severe sepsis (blood infection) and other inflammatory diseases. During sepsis, an uncontrolled infection leads to abnormal activation and localisation of important immune cells such as neutrophils and macrophages," said lead author Pranita P Sarangi, Assistant Professor at IIT Roorkee.
The researchers said that a dysfunctional immune response leads to deposition of such cells in visceral organs such as lung, kidney and liver causing multi-organ failure and death.
Sometimes, use of antibiotics against infections could even aggravate the condition by releasing broken components of bacteria into the blood which further activates our immune cells, they added.
In an animal model of sepsis, both the full length Fibulin-7 (Fbln7) protein and its C-terminal fragment (Fbln7C) inhibited macrophage and neutrophil infiltration to the inflamed tissues and organs such as peritoneal cavity and lungs.
The data, which is published in the journal FASEB, demonstrated that Fbln7 and its bioactive fragments or shorter peptides may have therapeutic potential for treating immuno-pathological conditions, which require negative regulation of immune cell functions.
The researchers said further research is currently ongoing on this aspect.
"Our immune system consists of varieties of white blood cells (WBCs) or leukocytes. In response to any inflammatory and infectious stimulus, leukocytes travelling in the blood vessels immediately respond by migrating to the affected site. While exiting the blood vessel and further travelling through the tissue spaces, activated WBCs interact with extracellular matrix proteins such as collagen and fibronectin," Sarangi said.
"The Immune cells bind to such proteins via their surface receptor molecules called integrins. These cell matrix communication through integrin receptors not only provide support for migration but also modulate various functions of the immune cells," she added.
Fibulins are a group of glycoproteins that are often associated with elastic fibres, basement membranes lining tissues and blood vessels, and other matrices.
Fbln7 was identified as the latest member of the fibulin family in developing tooth functioning as a cell adhesion molecule and has the ability to interact with other matrix proteins, receptors and growth factors. Fbln7 is also expressed in immune privileged tissues such as eye and placenta, but its functional significance was not known.
"In our study using human peripheral blood monocytes and an endotoxin induced systemic inflammation mouse model, we showed that Fbln7 and Fbln7C could inhibit adhesion, migration and production of inflammatory molecules from monocytes and macrophages," the researchers said.