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
Sign In
Advertise with Us


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

Download Mobile App


ATTENTION: Due to the COVID-19 PANDEMIC, many events are being rescheduled for a later date, converted into virtual venues, or altogether cancelled. Please check with the event organizer or website prior to planning for any forthcoming event.
22 May 2021 - 26 May 2021
Virtual Venue
25 May 2021 - 28 May 2021

New Control Mechanism Discovered in Innate Immune System

By LabMedica International staff writers
Posted on 11 Feb 2021
Print article
Image: Inter-α-inhibitor heavy chain 4 (ITIH4) inhibits proteases in the innate immune system via novel inhibitory mechanism (Photo courtesy of Rasmus Kjeldsen Jensen, PhD).
Image: Inter-α-inhibitor heavy chain 4 (ITIH4) inhibits proteases in the innate immune system via novel inhibitory mechanism (Photo courtesy of Rasmus Kjeldsen Jensen, PhD).
Proteases are enzymes that cleave other proteins. 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

Gold Supplier
Streptococcus Test
SARS-CoV-2/Influenza A+B/RSV/Adenovirus/M.Pneumoniae Antigen Combo Rapid Test
SARS-CoV-2/Influenza A+B/RSV/Adenovirus/M.Pneumoniae Antigen Combo Rapid Test
COVID-19 IgM/IgA/IgG Test
Silver Supplier
Disposable Viral Preservation Tube
Disposable Viral Preservation Tube

Print article
Mayo Medical Laboratories
BIOHIT  Healthcare OY


Molecular Diagnostics

view channel
Image: Photograph of the novel capsule-based smell test (Photo courtesy of Queen Mary University of London)

A Novel Capsule-Based Smell Test for Diagnosis of Neurological and Respiratory Diseases

To aid in diagnosing diseases where loss of the sense of smell is a symptom, such as in chronic neurological conditions like Parkinson's and Alzheimer's diseases and in acute respiratory infections such... Read more


view channel
Image: The Hamamatsu Photonics Nanozoomer 1 Digital Slide Scanner (Photo courtesy of University of Adelaide)

Genetic Background and Clinicopathologic Features Established for Adult-Onset Nephronophthisis

Nephronophthisis (NPH) is a genetic disorder of the kidneys which mainly affects children. It is classified as a medullary cystic kidney disease. The disorder is inherited in an autosomal recessive fashion... Read more


view channel
Image: DxA 5000 Fit (Photo courtesy of Beckman Coulter)

Beckman Coulter Becomes First Diagnostics Company to Offer Workflow Automation Specifically for Mid-Volume Laboratories

Beckman Coulter (Brea, CA, USA) has announced the global launch of the DxA 5000 Fit, a workflow-automation solution designed to fit into medium-sized labs that run fewer than 5,000 tests a day.... Read more
Copyright © 2000-2021 Globetech Media. All rights reserved.