Background: Eosinophil-associated RNases (EARs) are stored preformed in eosinophil cytoplasmic secretory granules and have a key role in eosinophil effector functions in host defence and inflammatory disorders. However, the secretion mechanisms of EARs are poorly understood.
Objective: Our study aimed to understand the involvement of cytoskeleton machinery in EAR secretion.
Methods: Fresh human and mouse eosinophils were stimulated with CCL11, and the secretion of enzymatically active EARs was detected using an RNase activity assay. The involvement of cytoskeletal elements or microtubules was probed using specific inhibitors.
Results: We found that dynamic polymerization of microtubules and cytoskeletal elements, such as Rho and Rac, is required for chemokine-mediated EAR secretion from human and mouse eosinophils. However, inhibition of ROCK (Rho-associated protein kinase) increased EAR secretion in human and mouse eosinophils even in the absence of chemokine stimulation, suggesting ROCK negatively regulates EAR secretion.
Conclusions: Collectively, these data suggest a cytoskeleton-dependent mechanism of EAR secretion from eosinophils, findings that are pertinent to host defence, allergy and other eosinophil-associated diseases.
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http://dx.doi.org/10.1111/cea.13292 | DOI Listing |
Methods Mol Biol
January 2025
Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
StarTrack is a powerful multicolor genetic tool designed to unravel cellular lineages arising from neural progenitor cells (NPCs). This innovative technique, based on retrospective clonal analysis and built upon the PiggyBac system, creates a unique and inheritable "color code" within NPCs. Through the stochastic integration of 12 distinct plasmids encoding six fluorescent proteins, StarTrack enables precise and comprehensive tracking of cellular fates and progenitor potentials.
View Article and Find Full Text PDFMethods Mol Biol
January 2025
Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
The HOX and PBX genes encode transcription factors that have key roles in development and cancer, both independently and as a heterodimer within a complex of proteins that recognizes specific sequences in DNA and can both activate and repress transcription of target genes. Due to functional redundancy amongst HOX proteins, knock down or knock out studies of individual genes often do not result in an altered phenotype. An alternative approach is to target the interaction between HOX and PBX proteins, which is dependent on a conserved hexapeptide region within HOX.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
January 2025
Department of Cardiovascular Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
It has been proposed that bone marrow contributes to the pathogenesis of arteriosclerosis. Nerve growth factor receptor (NGFR) is expressed in bone marrow stromal cells; it is also present in peripheral blood and ischemic coronary arteries. We hypothesized that bone marrow-derived NGFR-positive (NGFR) cells regulate arterial remodeling.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
January 2025
Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, Jiangsu Province, 214000, China.
Purpose: A novel theranostic radiopharmaceutical targeting prostate-specific membrane antigen (PSMA), [Ga]Ga/[Lu]Lu-NYM032, was developed and its diagnostic and therapeutic potential in the treatment of prostate cancer (PCa) was preliminarily evaluated.
Methods: The diagnostic efficacy of the PET tracer [Ga]Ga-NYM032 was first evaluated in PSMA-positive xenograft-bearing models (LNCaP models), followed by evaluation in 10 PCa patients using [Ga]Ga-PSMA617 a comparator. Finally, the therapeutic potential of [Lu]Lu-NYM032 was evaluated in LNCaP models.
J Virol
December 2024
Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
Protein kinase R (PKR) is an interferon-induced antiviral protein activated by autophosphorylation in response to double strand DNA (dsRNA) and other stimuli. Activated PKR causes translation inhibition and apoptosis, and it contributes to proinflammatory responses, cell growth, and differentiation. Mouse adenovirus type 1 (MAV-1) counteracts PKR by causing its degradation via a viral protein, early region 4 open reading frame 6 (E4orf6).
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