Immune reactions are characterized by the rapid immigration of phagocytes into sites of inflammation. Meticulous regulation of these migratory processes is crucial for preventing uncontrolled and harmful phagocyte extravasation. S100A8/S100A9 is the major calcium-binding protein complex expressed in phagocytes. After release, this complex acts as a proinflammatory alarmin in the extracellular space, but the intracellular functions of these highly abundant proteins are less clear. Results of this study reveal an important role of S100A8/S100A9 in coordinated cytoskeleton rearrangement during migration. We found that S100A8/S100A9 was able to cross-link F-actin and microtubules in a calcium- and phosphorylation-dependent manner. Cells deficient in S100A8/S100A9 showed abnormalities in cell adhesion and motility. Missing cytoskeletal interactions of S100A8/S100A9 caused differences in the surface expression and activation of β1-integrins as well as in the regulation of Src/Syk kinase family members. Loss of S100A8/S100A9 led to dysregulated integrin-mediated adhesion and migration, resulting in an overall higher dynamic activity of non-activated S100A8/S100A9-deficient phagocytes. Our data suggest that intracellular S100A8/S100A9 is part of a novel regulatory mechanism that ensures the precise control necessary to facilitate the change between the quiescent and activated state of phagocytes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045313 | PMC |
| http://dx.doi.org/10.3390/biomedicines11030835 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Metagenome-informed metaproteomics of the human gut microbiome, host, and dietary exposome uncovers signatures of health and inflammatory bowel disease.
Cell
January 2025
Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel; Division of Microbiome & Cancer, DKFZ, Heidelberg, Germany. Electronic address:
Host-microbiome-dietary interactions play crucial roles in regulating human health, yet their direct functional assessment remains challenging. We adopted metagenome-informed metaproteomics (MIM), in mice and humans, to non-invasively explore species-level microbiome-host interactions during commensal and pathogen colonization, nutritional modification, and antibiotic-induced perturbation. Simultaneously, fecal MIM accurately characterized the nutritional exposure landscape in multiple clinical and dietary contexts.
View Article and Find Full Text PDFRegulation of Age-Related Lipid Metabolism in Ovarian Cancer.
Int J Mol Sci
January 2025
Division of Reproductive Sciences, Department of Obstetrics and Gynecology, Duke University School of Medicine, 701 West Main Street, Suite 510, Duke, P.O. Box 90534, Durham, NC 27701, USA.
The mortality rate of ovarian cancer (OC) remains the highest among female gynecological malignancies. Advanced age is the highest risk factor for OC development and progression, yet little is known about the role of the aged tumor microenvironment (TME). We conducted RNA sequencing and lipidomic analysis of young and aged gonadal adipose tissue from rat xenografts before and after OC formation.
View Article and Find Full Text PDFBiomimetic nanostructural materials based on placental amniotic membrane-derived nanofibers for self-healing and anti-adhesion during cesarean section.
Biomaterials
January 2025
Translational Medicine Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China; Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, 511462, China. Electronic address:
Cesarean section (CS) is highly prevalent surgery among females. However, current absorbable anti-adhesion membranes used clinically can partially prevent postoperative adhesions but show limited efficacy in tissue regeneration, leaving post-cesarean women at risk for severe complications including cesarean scar pregnancy, placenta previa, and uterine rupture. Herein, we designed a fully amniotic membrane (AM)-derived biomimetic nanostructural materials (AM-BNMs) as an anti-adhesion barrier, and validated its therapeutic efficacy in a rat CS model.
View Article and Find Full Text PDFHDL Cholesterol-Associated Shifts in the Expression of Preselected Genes Reveal both Pro-Atherogenic and Atheroprotective Effects of HDL in Coronary Artery Disease.
Front Biosci (Landmark Ed)
November 2024
Laboratory of Human Molecular Genetics, National Research Center "Kurchatov Institute", 123182 Moscow, Russia.
Background: The associations of high-density lipoprotein (HDL) level and functionality with lipid metabolism, inflammation, and innate immunity in coronary artery disease (CAD) remain controversial. The differential expression of a set of genes related to HDL metabolism (24 genes) and atherogenesis (41 genes) in peripheral blood mononuclear cells (PBMC) from CAD and control patients with varied HDL cholesterol (HDL-C) levels was compared.
Methods: 76 male patients 40-60 years old with CAD diagnosed by angiography and 63 control patients were divided into three groups with low, normal (1.
EVA1B facilitates esophageal squamous carcinoma progression and recruitment of immunosuppressive myeloid-derived suppressor cells in the tumor microenvironment.
Pharmacol Res
December 2024
Department of Thoracic Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, China. Electronic address:
Article Synopsis
- EVA1B is found to be significantly up-regulated in esophageal squamous cell carcinoma (ESCC) tissues, linking it to advanced cancer stages and increased myeloid-derived suppressor cells (MDSCs).
- Silencing EVA1B leads to reduced proliferation and tumor growth in ESCC cells and mouse models, promoting apoptosis and disrupting cell cycle progression.
- The study suggests that targeting EVA1B could hinder both ESCC progression and MDSC activity, highlighting its potential as a therapeutic strategy for ESCC patients.
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!