ArticleThe Journal of clinical investigation1999
Proteolysis of monocyte CD14 by human leukocyte elastase inhibits lipopolysaccharide-mediated cell activation.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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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.
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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.
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Who cites it
41 citing papers in PubMed, 123 citations in OpenAlex.
- Soluble CD14 Levels Predict Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Independently of Obesity and Type 2 Diabetes.International journal of molecular sciences · 2026Article
- Innate Immunity in Cystic Fibrosis: Varied Effects of CFTR Modulator Therapy on Cell-to-Cell Communication.International journal of molecular sciences · 2025Review
- Low-Density Neutrophils: Enigmatic Cells in Health and Disease.Journal of immunology research · 2025Review
- A critical guideline for controlling monocyte-derived macrophages phenotypes.Frontiers in immunology · 2025Review
- Neutrophil Elastase Targets Select Proteins on Human Blood-Monocyte-Derived Macrophage Cell Surfaces.International journal of molecular sciences · 2024Article
- The Direct Anti-Virulence but Not Bactericidal Activity of Human Neutrophil Elastase againstInternational journal of molecular sciences · 2023Article
- Current Status of Antibiotic Stewardship and the Role of Biomarkers in Antibiotic Stewardship Programs.Infection & chemotherapy · 2022Review
- Article
- Leveling Up the Controversial Role of Neutrophils in Cancer: When the Complexity Becomes Entangled.Cells · 2021Review
- Neutrophil Elastase and Chronic Lung Disease.Biomolecules · 2021Review
- Neutrophil Elastase Defects in Congenital Neutropenia.Frontiers in immunology · 2021Review
- Targeting Neutrophils in Sepsis: From Mechanism to Translation.Frontiers in pharmacology · 2021Review
- Early Antiretroviral Therapy Prevents Viral Infection of Monocytes and Inflammation in Simian Immunodeficiency Virus-Infected Rhesus Macaques.Journal of virology · 2020Article
- The Metalloproteinase ADAMTS5 Is Expressed by Interstitial Inflammatory Cells in IgA Nephropathy and Is Proteolytically Active on the Kidney Matrix.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Neutrophil elastase promotes macrophage cell adhesion and cytokine production through the integrin-Src kinases pathway.Scientific reports · 2020Article
- Soluble CD14, Ischemic Stroke, and Coronary Heart Disease Risk in a Prospective Study: The REGARDS Cohort.Journal of the American Heart Association · 2020Article
- Alpha-1 Antitrypsin-A Target for MicroRNA-Based Therapeutic Development for Cystic Fibrosis.International journal of molecular sciences · 2020Review
- Magnesium sulfate inhibits binding of lipopolysaccharide to THP-1 cells by reducing expression of cluster of differentiation 14.Inflammopharmacology · 2019Article
- Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs.Cellular and molecular life sciences : CMLS · 2018Article
- Update on Neutrophil Function in Severe Inflammation.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human leukocyte elastase (HLE), a polymorphonuclear neutrophil (PMN) serine proteinase, is proteolytically active on some membrane receptors at the surface of immune cells. The present study focused on the effect of HLE on the expression of CD14, the main bacterial lipopolysaccharide (LPS) receptor at the surface of monocytes. HLE exhibited a time- and concentration-dependent downregulatory effect on CD14 surface expression. A 30-minute incubation of 3 microM HLE was required to display 95% disappearance of the receptor. This downregulation resulted from a direct proteolytic process, not from a shedding consecutive to monocyte activation as observed upon challenge with phorbol myristate acetate (PMA). To confirm that CD14 is a substrate for HLE, this enzyme was incubated with recombinant human CD14 (Mr approximately 57,000), and proteolysis was further analyzed by immunoblot analysis. Cleavage of the CD14 molecule was directly evidenced by the generation of short-lived fragments (Mr approximately 47,000 and 30,000). As a consequence of the CD14 proteolysis, a decrease in the responsiveness of monocytes to LPS was observed, as assessed by measuring tumor necrosis factor-alpha (TNF-alpha) formation. This inhibition was only observed with 1 ng/ml of LPS, i.e., when only the CD14-dependent pathway was involved. At a higher LPS concentration, such as 10 microgram/ml, when CD14-independent pathways were operative, this inhibition was overcome. The direct proteolysis by HLE of the membrane CD14 expressed on monocytes illustrates a potential anti-inflammatory effect of HLE through inhibition of LPS-mediated cell activation.
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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.