Diabetes is associated with dire peripheral sequelae including foot ulcers and amputations. A recent article by Wong et al. demystifies this connection by demonstrating that the neutrophil defense mechanism of extruding decondensed chromatin, termed NETosis, mediates delayed wound healing in diabetes and provides a therapeutic strategy for this indication.
- MeSH
- Citrulline metabolism MeSH
- Extracellular Traps * drug effects MeSH
- Wound Healing * drug effects MeSH
- Hydrolases genetics metabolism MeSH
- Diabetes Complications pathology MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
The process of forming and releasing neutrophil extracellular traps (NETs) can be regulated by exogenous and endogenous factors, including cytokines. The study aimed to assess the impact of proinflammatory cytokines, IL-15, IL-17, IL-18, and anti-inflammatory IL-10 on the formation of NETs, all in comparison to IL-8 and pathogenic factors: LPS, fMLP. Also, the expression of myeloperoxidase (MPO), one of the main elements of neutrophil traps, was evaluated. After isolating the neutrophils with Polymorphprep™, the cells were sorted using CD16 MACS® microbeads and incubated with selected factors. The formation of NETs was registered using a BD Pathway 855 microscope system and the expression of MPO was evaluated using flow cytometry. The amounts of circulating DNA in cell supernatants was fluorescently quantified. Microscopic photographs indicated that rhIL-15, rhIL-17, rhIL-18 and fMLP induce formation and release of NETs at a similar timespan, while in the presence of rhIL-10, the formation of the traps was delayed. The presence of the studied cytokines indicated two populations of neutrophils displaying differing MPO expression (MPOlow and MPOhigh). Moreover, stimulation of neutrophils with LPS and fMLP revealed two populations of these cells that differed not only in the expression of MPO, but also in size.
- MeSH
- Cytokines metabolism MeSH
- Interleukin-15 metabolism MeSH
- Interleukin-17 metabolism MeSH
- Interleukin-18 metabolism MeSH
- Humans MeSH
- Peroxidase metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The release of neutrophil extracellular traps (NETs) is one of the weapons neutrophils have in their armory. NETs consist of extracellular chromatin fibers decorated with a plethora of cytoplasmic and granular proteins, such as the antimicrobial serine protease neutrophil elastase (NE). Because the first description of NETs as beneficial to the host, reports on their double-faced role in health and disease have considerably increased recently. On one hand, NETs reportedly trap and kill bacteria and also participate in the resolution of the acute inflammation associated with infection and with tissue damage. On the other hand, numerous negative aspects of NETs contribute to the etiopathogenesis of autoimmune disorders. Employing soluble and solid fluorescent substrates, we demonstrate the interaction of NE with aggregated NETs (aggNETs), the limitation of its enzymatic activity and the containment of the enzyme from surrounding tissues. These events prevent the spread of inflammation and tissue damage. The detection of DNase 1-dependent elevation of NE activity attests the continuous presence of patrolling neutrophils forming NETs and aggNETs even under conditions physiologic conditions.
- MeSH
- Enzyme Activation MeSH
- Deoxyribonuclease I metabolism MeSH
- Deoxyribonucleases metabolism MeSH
- Extracellular Traps immunology metabolism MeSH
- Leukocyte Elastase metabolism MeSH
- Humans MeSH
- Mice MeSH
- Neutrophils immunology metabolism MeSH
- Body Fluids metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Interferon-alpha therapeutic use MeSH
- Carcinoid Tumor diagnosis epidemiology etiology pathology therapy MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Appendiceal Neoplasms surgery MeSH
- Neuroendocrine Tumors classification MeSH
- Somatostatin analogs & derivatives therapeutic use MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- MeSH
- Immunotherapy MeSH
- Clinical Trials as Topic MeSH
- Humans MeSH
- Neuroendocrine Tumors therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- News MeSH
- Keywords
- everolimusum, somatostatin oktreotid,
- MeSH
- Chemotherapy, Adjuvant MeSH
- Dacarbazine MeSH
- Adult MeSH
- Hospitalization MeSH
- Congresses as Topic MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Metastasis * MeSH
- Liver Neoplasms diagnosis therapy MeSH
- Lung Neoplasms * diagnosis drug therapy MeSH
- Pancreatic Neoplasms * diagnosis drug therapy MeSH
- Neuroendocrine Tumors * diagnosis epidemiology drug therapy classification MeSH
- Disease Progression MeSH
- Radionuclide Imaging utilization MeSH
- Radiotherapy MeSH
- Death MeSH
- Sunitinib MeSH
- Embolization, Therapeutic utilization MeSH
- Patient Care Team * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
