Related Experiment Video
Updated: Aug 14, 2025
09:23
Monitoring Neutrophil Elastase and Cathepsin G Activity in Human Sputum Samples
Published on: May 21, 2021
16.5K
Soluble Signal Inhibitory Receptor on Leukocytes-1 Is Released from Activated Neutrophils by Proteinase 3 Cleavage
Helen J von Richthofen1,2, Geertje H A Westerlaken1,2, Doron Gollnast1,2
1Center of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Journal of Immunology (Baltimore, Md. : 1950)
|January 13, 2023
Summary
Signal inhibitory receptor on leukocytes-1 (SIRL-1) is shed from activated neutrophils, releasing soluble SIRL-1 (sSIRL-1) and diminishing immune function. This shedding is mediated by proteinase 3 and occurs in patients with RSV bronchiolitis and COVID-19.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Signal inhibitory receptor on leukocytes-1 (SIRL-1) is an immune inhibitory receptor on granulocytes and monocytes that reduces antimicrobial functions.
- Previous studies showed decreased SIRL-1 on neutrophils in infants with RSV bronchiolitis and rapid loss upon in vitro activation.
Purpose of the Study:
- To investigate if activated neutrophils lose SIRL-1 via ectodomain shedding.
- To measure soluble SIRL-1 (sSIRL-1) levels in patients with RSV bronchiolitis and COVID-19.
- To elucidate the mechanism and regulation of SIRL-1 shedding.
Main Methods:
- Developed an ELISA to quantify sSIRL-1.
- Measured sSIRL-1 in sputum/plasma of RSV patients and serum of COVID-19 patients.
- Investigated sSIRL-1 release from in vitro activated neutrophils.
- Assessed the effect of proteinase 3 inhibition and Staphylococcus aureus extracellular adherence protein on shedding.
Main Results:
- sSIRL-1 concentrations were elevated in sputum from RSV patients and serum from COVID-19 patients compared to controls.
- In vitro activated neutrophils released sSIRL-1 through proteolytic cleavage, impairing SIRL-1's ability to inhibit reactive oxygen species production.
- SIRL-1 shedding was inhibited by proteinase 3 inhibitors and Staphylococcus aureus extracellular adherence protein.
Conclusions:
- SIRL-1 is released from activated neutrophils via proteinase 3 cleavage, resulting in detectable endogenous sSIRL-1 in vivo.
- SIRL-1 shedding diminishes neutrophil antimicrobial function.
- Staphylococcus aureus may counteract SIRL-1 shedding to maintain its inhibitory function.
More Related Videos
Related Concept Videos
01:25Selectins
3.4K
Cell adhesion is an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain,...
3.4K
01:22Amplifying Signals via Enzymatic Cascade
8.6K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.6K
01:11IP3/DAG Signaling Pathway
12.3K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
12.3K
02:26NF-κB-dependent Signaling Pathway
7.8K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.8K
01:28Nitric Oxide Signaling Pathway
5.1K
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.1K