Characterizing the anti-inflammatory and tissue protective actions of a novel Annexin A1 peptide
| العنوان: | Characterizing the anti-inflammatory and tissue protective actions of a novel Annexin A1 peptide |
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| المؤلفون: | Michele D'Amico, Mauro Perretti, Clara Di Filippo, Jesmond Dalli |
| المساهمون: | Perretti, Mauro, DI FILIPPO, Clara, D'Amico, Michele, Dalli, Jesmond |
| المصدر: | PLoS ONE, Vol 12, Iss 4, p e0175786 (2017) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Chemokine, Critical Care and Emergency Medicine, Phagocyte, Neutrophils, Anti-Inflammatory Agents, lcsh:Medicine, Apoptosis, Peptide, Pharmacology, Pathology and Laboratory Medicine, Biochemistry, White Blood Cells, Mice, Animal Cells, Annexin, Medicine and Health Sciences, lcsh:Science, Immune Response, Annexin A1, chemistry.chemical_classification, Phagocytes, Multidisciplinary, Cell Death, biology, Medicine (all), Neutrophil, 3. Good health, Anti-Inflammatory Agent, medicine.anatomical_structure, Cell Processes, Cellular Types, medicine.symptom, Research Article, Human, Agonist, Cardiotonic Agents, medicine.drug_class, Immune Cells, Inflammatory Diseases, Immunology, Human Umbilical Vein Endothelial Cell, Inflammation, Myocardial Reperfusion Injury, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, Human Umbilical Vein Endothelial Cells, medicine, Animals, Humans, Cardiotonic Agent, Efferocytosis, Adaptor Proteins, Signal Transducing, Blood Cells, Biochemistry, Genetics and Molecular Biology (all), business.industry, Animal, Macrophages, lcsh:R, Biology and Life Sciences, Cell Biology, Disease Models, Animal, 030104 developmental biology, chemistry, Agricultural and Biological Sciences (all), Reperfusion, biology.protein, lcsh:Q, Peptides, business |
| الوصف: | Inflammation in now appreciated to be at the centre of may diseases that affect Western civilization. Current therapeutics for managing these conditions may interfere with the host response leading to immune suppression. We recently developed an annexin (Anx) A1-derived peptide, coined CR-AnxA12-50, which displays potent pro-resolving and tissue protective actions. Herein, we designed a novel peptide using CR-AnxA12-50 as a template that was significantly more resistant to neutrophil-mediated degradation. This peptide, termed CR-AnxA12-48, retained high affinity and specificity to the pro-resolving Lipoxin A4 receptor (ALX) with an IC50 of ~20nM. CR-AnxA12-48 dose dependently (100fM-10nM) promoted the efferocytosis of apoptotic neutrophils, an action that was mediated by the murine orthologue of human ALX. The neutrophil-directed actions were also retained with human primary cells were CR-AnxA12-48 reduced human neutrophil recruitment to activated endothelial cells at concentrations as low as 100 pM. This protective action was mediated by human ALX, since incubation of neutrophils with an anti-ALX antibody reversed this anti-inflammatory actions of CR-AnxA12-48. Administration of this peptide to mice during dermal inflammation led to a significant and dose dependent decrease in neutrophil recruitment. This reduction in neutrophil numbers was more pronounced than that displayed by the parent peptide CR-AnxA12-50. CR-AnxA12-48 was also cardioprotecitve reducing infarct size and systemic chemokine (C-C motif) ligand 5 concentration following ischemia reperfusion injury. These findings identify CR-AnxA12-48 as a new ALX agonist that regulates phagocyte responses and displays tissue-protective actions. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::316733ab1e10eb57b3f2b897e8628a57Test http://europepmc.org/articles/PMC5391094?pdf=renderTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....316733ab1e10eb57b3f2b897e8628a57 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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