Features | Partner Sites | Information | LinkXpress
Sign In
Demo Company
GLOBETECH PUBLISHING LLC
PURITAN MEDICAL

Protease Found Crucial for First-Line Immune Defense Complement Activation Pathway

By BiotechDaily International staff writers
Posted on 04 Dec 2012
Scientists have established a lectin-associated protease to be central to the complement pathway activation. The discovery answers a long-standing question in immunology and opens new possibilities for manipulating the immune system in medical therapy.

In an international collaboration with scientists in the USA and Turkey, scientists at Denmark’s Aarhus University (Aarhus, Denmark) led the study mapping the mechanism underlying the lectin-pathway central to complement pathway activation. Activation of the lectin pathway of complement has been thought to occur via recognition of pathogens via mannan-binding lectin (MBL) or ficolins in complex with MBL-associated serine proteases (MASPs).

Using blood samples from a unique patient harboring a rare genetic syndrome, the researchers have now established that it is the enzyme MASP-1 that is key to activation of the complement system. In mice, MASP-1 and MASP-3 had been previously reported to be central also to alternative pathway function. The patient in the current study harbors a nonsense mutation in the common part of the MASP1 gene and hence is deficient in both MASP-1 and MASP-3. Surprisingly, the researchers found that the alternative pathway in this patient functions normally, and is unaffected by reconstitution with MASP-1 and MASP-3. Conversely, they found that the patient has a nonfunctional lectin pathway, which can be restored by MASP-1, implying that this component is crucial for complement activation. Additional findings further established the central role of MASP-1. MASP-1 is able to efficiently auto-activate, for example when it senses a bacterium; it then activates MASP-2, which in turn activates the rest of the complement system cascade that attacks the bacteria.

The discovery may have implications for the treatment of various medical conditions, including cancer and stroke patients. "For example this system is important for the survival of patients undergoing chemotherapy, because this treatment suppresses other functions of the immune system - so in their case it is beneficial to "rev up" the system.
But following a heart attack there may be reasons to instead dampen the system. The complement system has an unfortunate tendency to attack tissues that have suffered damage due to deprivation of oxygen, and thereby it exacerbates the damage already done to the heart,” explained Dr. Soeren Egedal Degn, first author and postdoc at Aarhus University.

The findings were published October 15, 2012, in the Journal of Immunology.

Related Links:
Aarhus University



Channels

Drug Discovery

view channel
Image: Cancer cells were treated with a control (left) and the overstimulating compound MCB-613 (right) (Photo courtesy of Dr. Lei Wang, Baylor University College of Medicine).

Drug Candidate Propels Cancer Cells into Fatal Overdrive

A candidate drug that destroys cancer cells by stimulating them to produce more proteins than the cells can actually process was shown to kill a wide variety of cancer cells in culture and to inhibit tumor... Read more

Lab Technologies

view channel
Image: The Synergy Neo2 Multi-Mode Reader recently received Cisbio HTRF certification (Photo courtesy of BioTek Instruments Inc.).

High-Speed Multimode Microplate Reader Receives Homogenous Time-Resolved Fluorescence Certification

A new high-performance, high-speed microplate reader has received HTRF (homogenous time-resolved fluorescence) accreditation that certifies that it complies with standards for detection set by a major... Read more

Business

view channel

Innovative Microbial Diagnostics Developer Acquired by Biomedical Giant

A biotech company noted for its development of innovative products in the field of molecular microbiology diagnostics has been acquired by one of the world's largest biomedical corporations. GeneWEAVE BioSciences, Inc.(Los Gatos, CA, USA) and Roche (Basel, Switzerland) have announced that Roche will be purchasing the... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.