We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
LGC Clinical Diagnostics

THERMO FISHER SCIENTIFIC

Thermo Fisher Scientific provides analytical instruments, lab equipment, specialty diagnostics, reagents and integrat... read more Featured Products: More products

Download Mobile App




New Control Mechanism Discovered in Innate Immune System

By LabMedica International staff writers
Posted on 11 Feb 2021
Proteases are enzymes that cleave other proteins. More...
Most often, proteases occur in cascade networks, where a particular event triggers a chain reaction in which several proteases cleave and thereby activate each other. Most well-known is probably the coagulation cascade, which causes clotting of our blood when a vessel is punctured.

Inter-α-inhibitor heavy chain 4 (ITIH4) is a liver-produced plasma protein belonging to the inter–α-inhibitor/ITIH family of proteins that consists of bikunin and six different heavy chain proteins. This protein family is also referred to as inter–α-trypsin inhibitor proteins since bikunin displays a weak inhibitory effect on proteases for which a biological role is yet to be defined.

Biomedical Scientists at Aarhus University (Aarhus, Denmark) and a colleague investigated which other proteins in the blood the so-called mannan-binding lectin–associated serine protease (MASP) proteases interact with the complement cascade. To characterize in detail how ITIH4 inhibits the MASP proteases, they isolated both free ITIH4 and ITIH4 bound to the MASP-1 protease. By the use of X-ray small-angle scattering and electron microscopy, these samples were studied. Liquid chromatography tandem-mass spectrometry was performed using a Q-Exactive plus mass spectrometer (ThermoFisher Scientific, Waltham, MA, USA).

The scientists showed that ITIH4 is cleaved by several human proteases within a protease-susceptible region, enabling ITIH4 to function as a protease inhibitor. This is exemplified by its inhibition of mannan-binding lectin–associated serine protease-1 (MASP-1), MASP-2, and plasma kallikrein, which are key proteases for intravascular host defense. Mechanistically, ITIH4 acts as bait that, upon cleavage, forms a non-covalent, inhibitory complex with the executing protease that depends on the ITIH4 von Willebrand factor A domain. ITIH4 inhibits the MASPs by sterically preventing larger protein substrates from accessing their active sites, which remain accessible and fully functional toward small substrates.

The authors concluded that the active sites of MASP within the non-covalent ITIH4-MASP complexes are catalytically competent, but downstream cleavage of C2 and C4 are inhibited by physically blocking access of the scissile bonds to the active sites. Such activity was demonstrated in human and murine serum. ITIH4 was found to be cleaved by various proteases within the protease-susceptible region (PSR), suggesting that ITIH4 is a broad-acting inhibitor that targets numerous proteases. The study was published on January 8, 2021 in the journal Science Advances.

Related Links:
Aarhus University
ThermoFisher Scientific



New
Gold Member
Quality Control Material
iPLEX Pro Exome QC Panel
3-Part Differential Hematology Analyzer
Swelab Alfa Plus Sampler
New
Gold Member
Serological Pipets
INTEGRA Serological Pipets
New
Celiac Disease Test
Anti-Gliadin IgG ELISA
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








Channels

Hematology

view channel
Image: CitoCBC is the world first cartridge-based CBC to be granted CLIA Waived status by FDA (Photo courtesy of CytoChip)

Disposable Cartridge-Based Test Delivers Rapid and Accurate CBC Results

Complete Blood Count (CBC) is one of the most commonly ordered lab tests, crucial for diagnosing diseases, monitoring therapies, and conducting routine health screenings. However, more than 90% of physician... Read more

Immunology

view channel
Image: A simple blood test could replace surgical biopsies for early detecion of heart transplant rejection (Photo courtesy of Shutterstock)

Blood Test Detects Organ Rejection in Heart Transplant Patients

Following a heart transplant, patients are required to undergo surgical biopsies so that physicians can assess the possibility of organ rejection. Rejection happens when the recipient’s immune system identifies... Read more

Pathology

view channel
These images illustrate how precision oncology Organ Chips recapitulate individual patients’ responses to chemotherapy (Photo courtesy of Wyss Institute at Harvard University)

Cancer Chip Accurately Predicts Patient-Specific Chemotherapy Response

Esophageal adenocarcinoma (EAC), one of the two primary types of esophageal cancer, ranks as the sixth leading cause of cancer-related deaths worldwide and currently lacks effective targeted therapies.... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.