ArticleScientific reports2016
Phenol-soluble modulin α4 mediates Staphylococcus aureus-associated vascular leakage by stimulating heparin-binding protein release from neutrophils.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04313790 (Assessment of the Anti-inflammatory Effect of Unfractionated Heparin Administered Either by Intravenous Infusion Versus Subcutaneous Injection in Critically Ill Septic Patients. A Randomized Controlled Trial), which is not on this map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Assessment of the Anti-inflammatory Effect of Unfractionated Heparin Administered Either by Intravenous Infusion Versus Subcutaneous Injection in Critically Ill Septic Patients. A Randomized Controlled Trial
Who cites it
27 citing papers in PubMed, 31 citations in OpenAlex.
- Microbe-Derived Antimicrobial Peptides: Immunomodulation and Gut Microbiota Homeostasis.Microorganisms · 2026Review
- Staphylococcus aureus-vascular endothelium interactions: Mechanisms and therapeutic opportunities.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Review
- Potential Compounds as Inhibitors of Staphylococcal Virulence Factors Involved in the Development of Thrombosis.Toxins · 2025Review
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- Immunoinformatics design of an mRNA vaccine against classical swine fever virus using conserved E2 protein and NS3 T-lymphocyte epitopes.BioImpacts : BI · 2025Article
- The Purine Biosynthesis Repressor, PurR, Contributes to Vancomycin Susceptibility of Methicillin-resistant Staphylococcus aureus in Experimental Endocarditis.The Journal of infectious diseases · 2024Article
- Article
- Competitive inhibition and mutualistic growth in co-infections: decipheringISME communications · 2024Article
- An inflammatory paradox: strategies inflammophilic oral pathobionts employ to exploit innate immunity via neutrophil manipulation.Frontiers in oral health · 2024Article
- Baicalin Attenuates Panton-Valentine Leukocidin (PVL)-Induced Cytoskeleton Rearrangement via Regulating the RhoA/ROCK/LIMK and PI3K/AKT/GSK-3β Pathways in Bovine Mammary Epithelial Cells.International journal of molecular sciences · 2023Article
- Designing a Next-Generation Multiepitope-Based Vaccine againstPathogens (Basel, Switzerland) · 2023Article
- [Changes of heparin-binding protein in severe burn patients during shock stage and its effects on human umbilical vein endothelial cells and neutrophils].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2022Observational
- Heparin-binding protein-enhanced quick SOFA score improves mortality prediction in sepsis patients.Frontiers in medicine · 2022Article
- Article
- Development of a Conserved Chimeric Vaccine for Induction of Strong Immune Response againstVaccines · 2021Article
- Increased Antibiotic Resistance of Methicillin-ResistantJournal of microbiology and biotechnology · 2021Article
- Fpr2/CXCL1/2 Controls Rapid Neutrophil Infiltration to InhibitFrontiers in immunology · 2021Article
- Article
- Manipulating neutrophil degranulation as a bacterial virulence strategy.PLoS pathogens · 2020Review
- Exotoxins from Staphylococcus aureus activate 5-lipoxygenase and induce leukotriene biosynthesis.Cellular and molecular life sciences : CMLS · 2020Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular leakage frequently occurs in patients with severe Staphylococcus aureus infection. However, the mechanism underlying S. aureus infection-induced vascular leakage remains unclear. Here, we identified the S. aureus virulence factor phenol-soluble modulin (PSM)α4 from the culture supernatant of strain USA300 as a stimulator of heparin-binding protein (HBP) release from polymorphonuclear neutrophils (PMNs) and demonstrated that PSMα4-induced HBP release from PMNs leads to vascular leakage. PSMα4 appeared less cytolytic than PSMα1-3 and was insensitive to lipoproteins; it significantly increased myeloperoxidase and elastase release from PMNs and cell surface CD63 expression in PMNs. PSMα4-induced HBP release required formyl peptide receptor 2 (FPR2) and phosphoinositide 3-kinase (PI3K) and depended on Ca(2+) influx and cytoskeleton rearrangement. Thus, PSMα4 may stimulate HBP release by activating FPR2 and PI3K to initiate PMN degranulation. PSMα4-induced HBP release from PMNs increased endothelial cell monolayer permeability in vitro and induced vascular leakage in mice. This novel function of PSMα4 may contribute to the pathogenesis of S. aureus and may be a potential therapeutic target.
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