ROS Activated NETosis of Bone Marrow CD55+ Intermediate Mature Neutrophils Through HIF1α-PADI4 Pathway to Initiate Bone Aging.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE273832 | GEO | 2025/12/02
REPOSITORIES: GEO
Similar Datasets
Project description:ROS Activated NETosis of Bone Marrow CD55+ Intermediate Mature Neutrophils Through HIF1α-PADI4 Pathway to Initiate Bone Aging.
| PRJNA1143433 | ENA
Project description:The critical size for strong interaction of hydrophobic particles with phospholipid bilayers has been predicted to be 10 nm. Because of the wide spreading of nonpolar nanoparticles (NPs) in the environment, we aimed to reveal the ability of living organisms to entrap NPs via formation of neutrophil extracellular traps (NETs). Upon interaction with various cell types and tissues, 10- to 40-nm-sized NPs induce fast (<20 min) damage of plasma membranes and instability of the lysosomal compartment, leading to the immediate formation of NETs. In contrast, particles sized 100-1,000 nm behaved rather inertly. Resulting NET formation (NETosis) was accompanied by an inflammatory reaction intrinsically endowed with its own resolution, demonstrated in lungs and air pouches of mice. Persistence of small NPs in joints caused unremitting arthritis and bone remodeling. Small NPs coinjected with antigen exerted adjuvant-like activity. This report demonstrates a cellular mechanism that explains how small NPs activate the NETosis pathway and drive their entrapping and resolution of the initial inflammatory response.
| S-EPMC5056044 | biostudies-literature
Project description:Neutrophil homeostasis is maintained, in part, by the regulated release of neutrophils from the bone marrow. Constitutive expression of the chemokine CXCL12 by bone marrow stromal cells provides a key retention signal for neutrophils in the bone marrow through activation of its receptor CXCR4. Herein, we show that the ELR chemokines CXCL1 and CXCL2 are constitutively expressed by bone marrow endothelial cells and osteoblasts, and CXCL2 expression is induced in endothelial cells during granulocyte colony-stimulating factor (G-CSF)-induced neutrophil mobilization. Neutrophils lacking CXCR2, the receptor for CXCL1 and CXCL2, are preferentially retained in the bone marrow, reproducing a myelokathexis phenotype. Transient disruption of CXCR4 failed to mobilize CXCR2 neutrophils. However, doubly deficient neutrophils (CXCR2-/- CXCR4-/-) displayed constitutive mobilization, showing that CXCR4 plays a dominant role. Collectively, these data suggest that CXCR2 signaling is a second chemokine axis that interacts antagonistically with CXCR4 to regulate neutrophil release from the bone marrow. We used gene expression microarrays to determine the changes in osteoblasts and bone marrow endothelial cells after G-CSF treatment. 3 untreated and G-CSF-treated osteoblast samples and 4 untreated and G-CSF-treated endothelial samples.
2010-07-14 | E-GEOD-22925 | biostudies-arrayexpress
Project description:Transcriptional profile of bone marrow mature neutrophils
| PRJNA973587 | ENA
Project description:Generation of organ-infiltrating neutrophils occurs in hematopoietic tissues and organs, such as bone marrow and spleen, in response to tumor- and host-derived factors. The de novo expanded neutrophils then egress from hematopoietic sites, circulate through the blood vessels and infiltrate into the organ interstitia and parenchyma. During above trafficking process, neutrophils can undergo phenotypic and functional changes in response to tissue environments. To determine the difference among neutrophils residing in the hematopoietic site—BM, circulating in the blood, and those infiltrating in the metastatic organ, the transcriptional profiles of neutrophils were analyzed by RNA sequencing. 4T1 cells were injected into the fourth mammary fat pads of female syngeneic BALB/cJ mice (8-week-old, n = 3). At day 10 (pre-metastatic stage), the mice were euthanized and then CD45+CD11b+Ly6G<high>Ly6C<med> neutrophils from bone marrow (BM), peripheral blood (PB) and lung were isolated by fluorescence-activated cell sorting. Total RNA was isolated from neutrophils using the miRNeasy Mini kit (Qiagen) and the transcriptional profiles of neutrophils were analyzed by RNA sequencing
2020-07-24 | E-MTAB-9128 | biostudies-arrayexpress
Project description:Neutrophil homeostasis is maintained, in part, by the regulated release of neutrophils from the bone marrow. Constitutive expression of the chemokine CXCL12 by bone marrow stromal cells provides a key retention signal for neutrophils in the bone marrow through activation of its receptor CXCR4. Herein, we show that the ELR chemokines CXCL1 and CXCL2 are constitutively expressed by bone marrow endothelial cells and osteoblasts, and CXCL2 expression is induced in endothelial cells during granulocyte colony-stimulating factor (G-CSF)-induced neutrophil mobilization. Neutrophils lacking CXCR2, the receptor for CXCL1 and CXCL2, are preferentially retained in the bone marrow, reproducing a myelokathexis phenotype. Transient disruption of CXCR4 failed to mobilize CXCR2 neutrophils. However, doubly deficient neutrophils (CXCR2-/- CXCR4-/-) displayed constitutive mobilization, showing that CXCR4 plays a dominant role. Collectively, these data suggest that CXCR2 signaling is a second chemokine axis that interacts antagonistically with CXCR4 to regulate neutrophil release from the bone marrow. We used gene expression microarrays to determine the changes in osteoblasts and bone marrow endothelial cells after G-CSF treatment.
2010-07-14 | GSE22925 | GEO
Project description:Pneumonia caused by Streptococcus pneumoniae is a leading cause of death worldwide, and bacterial resistance to antimicrobial drugs has become a major issue. A growing body of evidence indicates that the successful treatment of bacterial infections results from synergy between antibiotic-mediated direct antibacterial activity and the host’s immune defenses. However, the mechanisms underlying the protective immune responses induced by amoxicillin (a β-lactam antibiotic used as the first-line treatment of S. pneumoniae infections) have not been characterized. A better understanding of amoxicillin’s effects on host-pathogen interactions might facilitate the development of other treatment options. Given the crucial role of neutrophils in the control of S. pneumoniae infections, we decided to investigate amoxicillin’s impact on neutrophil development in a mouse model of pneumococcal superinfection. Although a single therapeutic dose of amoxicillin prevented local and systemic inflammatory responses, it did not impair the emergency granulopoiesis triggered in the bone marrow by S. pneumoniae. Importantly, treatment of pneumonia with amoxicillin was associated with a greater mature neutrophil count in the bone marrow; these neutrophils had specific transcriptomic and proteomic profiles. Furthermore, amoxicillin-conditioned, mature neutrophils in the bone marrow had a less activated phenotype and might be rapidly mobilized in peripheral tissues in response to systemic inflammation. Thus, by revealing a novel effect of amoxicillin on the development and functions of bone marrow neutrophils during Streptococcus pneumoniae pneumonia, our findings provide new insights into the impact of amoxicillin treatment on host immune responses.
2023-10-09 | PXD042496 | Pride
Project description:Osteocytes are the main cells in mineralized bone tissue. Elevated osteocyte apoptosis has been observed in lytic bone lesions of patients with multiple myeloma. However, their precise contribution to bone metastasis remains unclear.Here, we investigated the pathogenic mechanisms driving melanoma-induced osteocyte death. Both in vivo models and in vitro assays were combined with untargeted RNA sequencing approaches to explore the pathways governing melanoma-induced osteocyte death. We could show that ferroptosis is the primary mechanism behind osteocyte death in the context of melanoma bone metastasis. HMOX1 was identified as a crucial regulatory factor in this process, directly involved in inducing ferroptosis and affecting osteocyte viability. We uncover a non-canonical pathway that involves excessive autophagy-mediated ferritin degradation, highlighting the complex relationship between autophagy and ferroptosis in melanoma-induced osteocyte death. In addition, HIF1α pathway was shown as an upstream regulator, providing a potential target for modulating HMOX1 expression and influencing autophagy-dependent ferroptosis. In conclusion, our study provides insight into the pathogenic mechanisms of osteocyte death induced by melanoma bone metastasis, with a specific focus on ferroptosis and its regulation. This would enhance our comprehension of melanoma-induced osteocyte death.
2024-11-24 | GSE276370 | GEO
Project description:Purpose: Investigate the neutrophils could exspress different mRNA de novo from PGE2 stimulation. Methods: Isolated bone marrow neutrophils with Percoll gradient are treated with 10 μM of PGE2 for 24 hours. Results: Qualified sequence reads per sample to the mouse genome (mm10) with Bowtie2 or STAR were processed with StringTie and identified genes. Conclusion : 1,359 genes were significantly different in PGE2 treated bone marrow neutrophils from vehicle treated ones.
2022-08-01 | GSE199773 | GEO
Project description:Proteome profiles of isolated peripheral human neutrophils pretreated with purified Tamm-Horsfall protein and stimulated to undergo NETosis with PMA.
2024-09-23 | PXD045468 | Pride