JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Lung endothelial cell senescence impairs barrier function and promotes neutrophil adhesion and migration

  • 0Department of Molecular Pharmacology and Physiology, University of South Florida, Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL, USA.
Geroscience +

|

January 15, 2025

|

January 15, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Cellular senescence in lung endothelial cells weakens cell junctions and barrier function. This promotes inflammation and neutrophil migration, contributing to age-related lung dysfunction.

Area Of Science

  • Gerontology
  • Cell Biology
  • Pulmonology

Background

  • Cellular senescence, marked by irreversible cell cycle arrest, contributes to aging-related inflammation and organ dysfunction.
  • Senescence exhibits varied morphological and functional impacts across different cell types and organs.

Purpose Of The Study

  • To investigate cellular senescence markers in aged lungs and lung endothelial cells (ECs).
  • To determine the functional consequences of lung EC senescence on barrier integrity and inflammatory cell interactions.

Main Methods

  • Examined senescence markers (p21, γH2AX, SA-β-Gal, Ki-67, Lamin B1) in aged human and mouse lungs and cultured mouse lung ECs.
  • Induced senescence using SAHA or DOXO in cultured ECs.
  • Assessed EC barrier function via solute permeability and evaluated neutrophil chemotaxis and migration.

Main Results

  • Aged lungs and senescent ECs showed increased p21, γH2AX, SA-β-Gal and decreased Ki-67, Lamin B1.
  • Senescence correlated with lung inflammation, neutrophil infiltration, and altered junction proteins (VE-cadherin, ZO-1).
  • Senescent ECs displayed impaired barrier function and promoted neutrophil migration.

Conclusions

  • Lung EC senescence compromises endothelial barrier integrity by weakening cell-cell junctions.
  • Senescent lung ECs contribute to inflammation by promoting neutrophil adhesion and migration.
  • Lung EC senescence may drive age-related pulmonary inflammation and pathology.

Keywords:

Related Concept Videos

Selectins 01:25

3.2K

Cell adhesion is  an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain,...

Adherens Junctions 01:24

4.7K

Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types –  adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as  epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as  heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic

Regulation of Angiogenesis and Blood Supply 01:24

2.5K

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...