Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
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: A new micelle delivery system for the protective polyphenols resveratrol and quercetin (mRQ) may have value in cancer chemotherapy (Photo courtesy of Oregon State University).

Micelles Containing Resveratrol and Quercetin Reverse Doxorubicin Cardiotoxicity

Cancer researchers blocked the toxic effects of the cancer drug doxorubicin (DOX) by administering it together with the plant antioxidants resveratrol and quercetin. Although in use for more than 40... Read more

Lab Technologies

view channel
Image: The Leica DM2500 LED Microscope for clinical laboratories and research applications (Photo courtesy of Leica Microsystems).

New LED Microscope Completes Line of Clinical and Research Tools

A popular microscope used for both clinical and research applications is now available with LED illumination. The Leica (Wetzlar, Germany) DM2500 and DM2500 LED microscopes represent a class of tools... Read more

Business

view channel

Teva Buys Allergan Generic Business Unit

Teva Pharmaceutical Industries (Petah Tikva, Israel) has bought the Allergan (Irvine, CA, USA) generic drugs business for USD 40.5 billion in cash and stock, solidifying its position as the world's largest generic drug maker. Under the terms of the agreement, Teva will pay USD 33.75 billion in cash and USD 6.... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.