ArticleJournal of cellular and molecular medicine2022
CD44/ERM/F-actin complex mediates targeted nuclear degranulation and excessive neutrophil extracellular trap formation during sepsis.
Article in Journal of cellular and molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- Cytoskeleton proteins, the structural basis of T-lymphocyte and TEC restructure during rapid thymus regeneration.Histology and histopathology · 2025Review
- Hemoglobin glycation index and neutrophil percentage as predictors of congestive heart failure among individuals diagnosed with sepsis: A MIMIC-IV cohort study.Scientific reports · 2025Article
- Baicalin Modulates GlycolysisMediators of inflammation · 2025Article
- The dual role of neutrophils in sepsis-associated liver injury.Frontiers in immunology · 2025Review
- Targeted nuclear degranulation of neutrophils promotes the progression of pneumonia in ulcerative colitis.Precision clinical medicine · 2024Article
- Integrating molecular and cellular components of endothelial shear stress mechanotransduction.American journal of physiology. Heart and circulatory physiology · 2024Review
- Communications between Neutrophil-Endothelial Interaction in Immune Defense against Bacterial Infection.Biology · 2024Review
- CD44: a cancer stem cell marker and therapeutic target in leukemia treatment.Frontiers in immunology · 2024Review
- Unveiling Differential Responses of Granulocytes to Distinct Immunostimulants with Implications in Autoimmune Uveitis.Biomedicines · 2023Article
- Molecular basis of PIP2-dependent conformational switching of phosphorylated CD44 in binding FERM.Biophysical journal · 2023Article
- Neutrophil extracellular traps primed intercellular communication in cancer progression as a promising therapeutic target.Biomarker research · 2023Review
- [The characteristics of neutrophil extracellular traps produced by all-trans retinoic acid-induced dHL-60 under PMA stimulation].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2022Article
- CD44/ERM/F-actin complex mediates targeted nuclear degranulation and excessive neutrophil extracellular trap formation during sepsis.Journal of cellular and molecular medicine · 2022Article
- Neutrophil extracellular traps contribute to myofibroblast differentiation and scar hyperplasia through the Toll-like receptor 9/nuclear factor Kappa-B/interleukin-6 pathway.Burns & trauma · 2022Article
- Pathogen spectrum identified by targeted nanopore sequencing and exploratory analysis of hematological biomarkers in suspected intracranial infections.Frontiers in neurologyArticle
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Neutrophils release neutrophil extracellular traps (NETs) to capture and kill pathogens, but excessive NET release can damage the surrounding tissues. Myeloperoxidase (MPO) and neutrophil elastase (NE) are thought to be important in promoting histone depolymerization and DNA breakage in the nucleus. However, the detailed path by which MPO and NE enter the nucleus is unknown. In the present study, we observed that delayed fusion of azurophilic granules with the nuclear membrane 15-20 min after extracellular degranulation in activated neutrophils. In a subsequent experiment, we further demonstrated that this fusion leads to MPO entry into the nucleus and promotes nuclear histone depolymerization and DNA breakage, a process called 'targeted nuclear degranulation'. This process can be effectively inhibited by dexamethasone and accompanied by the continuous low levels of MPO in the nucleus after PMA stimulation. Meanwhile, we found that 'targeted nuclear degranulation' is dependent on the CD44 translocation and subsequent redistribution of CD44 / ERM (Ezrin/Radixin/Moesin) / F-actin complexes, which guides the movement of azurophilic granules towards the nucleus. Application of ERM phosphorylation inhibitors and importin activity inhibitors significantly reduced the complexes formation and redistribution. Taken together, these findings indicate for the first time that delayed 'targeted nuclear degranulation' after neutrophil activation is a key mechanism of NET formation. CD44/ERM/F-actin complex mediates this process, which providing targets with promising prospects for the precise regulation of NET formation.
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