ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Proteolytic activation transforms heparin cofactor II into a host defense molecule.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Review
- Clinical Trial Subgroup Analyses to Investigate Clinical and Immunological Outcomes of Convalescent Plasma Therapy in Severe COVID-19.Mayo Clinic proceedings. Innovations, quality & outcomes · 2022Article
- Predictive value of proteomic markers for advanced rectal cancer with neoadjuvant chemoradiotherapy.BMC cancer · 2022Article
- Zone of Interaction Between the Parasite and the Host: Protein Profile of the Body Cavity Fluid of Gasterosteus aculeatus L. Infected with the Cestode Schistocephalus solidus (Muller, 1776).Acta parasitologica · 2021Article
- System-wide molecular dynamics of endothelial dysfunction in Gram-negative sepsis.BMC biology · 2020Article
- Antithrombin: An anticoagulant, anti-inflammatory and antibacterial serpin.Journal of thrombosis and haemostasis : JTH · 2020Article
- An ecoimmunological approach to study evolutionary and ancient links between coagulation, complement and Innate immunity.Virulence · 2018Article
- Heparinase Is Essential for Pseudomonas aeruginosa Virulence during Thermal Injury and Infection.Infection and immunity · 2018Article
- Immunohaemostasis: a new view on haemostasis during sepsis.Annals of intensive care · 2017Review
- The Role of Heparin Cofactor Ⅱ in the Regulation of Insulin Sensitivity and Maintenance of Glucose Homeostasis in Humans and Mice.Journal of atherosclerosis and thrombosis · 2017Article
- Aggregation of thrombin-derived C-terminal fragments as a previously undisclosed host defense mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects.Scientific reports · 2017Article
- Thrombin-Derived Host-Defense Peptides Modulate Monocyte/Macrophage Inflammatory Responses to Gram-Negative Bacteria.Frontiers in immunology · 2017Article
- Role of Aromatic Amino Acids in Lipopolysaccharide and Membrane Interactions of Antimicrobial Peptides for Use in Plant Disease Control.The Journal of biological chemistry · 2016Article
- Pseudomonas aeruginosa elastase cleaves a C-terminal peptide from human thrombin that inhibits host inflammatory responses.Nature communications · 2016Article
- Reactive Center Loop (RCL) Peptides Derived from Serpins Display Independent Coagulation and Immune Modulating Activities.The Journal of biological chemistry · 2016Article
- Antimicrobial effects of helix D-derived peptides of human antithrombin III.The Journal of biological chemistry · 2014Article
- Discovery of modulators of HIV-1 infection from the human peptidome.Nature reviews. Microbiology · 2014Review
- A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive Pseudomonas aeruginosa infection.PloS one · 2014Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The abundant serine proteinase inhibitor heparin cofactor II (HCII) has been proposed to inhibit extravascular thrombin. However, the exact physiological role of this plasma protein remains enigmatic. In this study, we demonstrate a previously unknown role for HCII in host defense. Proteolytic cleavage of the molecule induced a conformational change, thereby inducing endotoxin-binding and antimicrobial properties. Analyses employing representative peptide epitopes mapped these effects to helices A and D. Mice deficient in HCII showed increased susceptibility to invasive infection by Pseudomonas aeruginosa, along with a significantly increased cytokine response. Correspondingly, decreased levels of HCII were observed in wild-type animals challenged with bacteria or endotoxin. In humans, proteolytically cleaved HCII forms were detected during wounding and in association with bacteria. Thus, the protease-induced uncovering of cryptic epitopes in HCII, which transforms the molecule into a host defense factor, represents a previously unknown regulatory mechanism in HCII biology and innate immunity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.