Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC
PZ HTL SA

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



BIOSIGMA S.R.L.
SLAS - Society for Laboratory Automation and Screening
RANDOX LABORATORIES
comments powered by Disqus

Channels

Drug Discovery

view channel

Omega 3 Found to Improve Behavior in Children with ADHD

Supplements of the fatty acids omega 3 and 6 can help children and adolescents who have a specific kind of have attention deficit hyperactivity disorder (ADHD). Moreover, these findings indicate that a customized cognitive training program can improve problem behavior in children with ADHD. Statistics show that 3%–6%... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Lab Technologies

view channel
Image: On target: When researchers introduced nanobodies they made to cells engineered to express a tagged version of a protein in skeletal fibers known as tubulin (red), the nanobodies latched on. The cells above have recently divided (Photo courtesy of Rockefeller University).

Turning Antibodies into Precisely Tuned Nanobodies

New technology has the potential to create nanobodies making them much more accessible than antibodies for all sorts of research. Antibodies control the process of recognizing and zooming in on molecular... Read more

Business

view channel

Two Industry Partnerships Initiated to Fuel Neuroscience Research

Faster, more complex neural research is now attainable by combining technology from two research companies. Blackrock Microsystems, LLC (Salt Lake City, UT, USA), a developer of neuroscience research equipment, announced partnerships with two neuroscience research firms—PhenoSys, GmbH (Berlin, Germany) and NAN Instruments, Ltd.... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.