Rho and Rac, but not ROCK, are required for secretion of human and mouse eosinophil-associated RNases.

Clin Exp Allergy

Division of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Published: February 2019

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353669PMC
http://dx.doi.org/10.1111/cea.13292DOI Listing

Publication Analysis

Top Keywords

human mouse
16
secretion human
12
mouse eosinophils
12
ear secretion
12
rho rac
8
eosinophil-associated rnases
8
host defence
8
cytoskeletal elements
8
secretion
6
ear
5

Similar Publications

StarTrack: Mapping Cellular Fates with Inheritable Color Codes.

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 PDF

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 PDF

Bone Marrow-derived NGFR-positive Dendritic Cells Regulate Arterial Remodeling.

Am 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 PDF

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.

View Article and Find Full Text PDF

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).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!