Related Experiment Videos

Endothelial microvesicles carrying Src-rich cargo impair adherens junction integrity and cytoskeleton homeostasis

Victor Chatterjee1, Xiaoyuan Yang1, Yonggang Ma1

  • 1Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.

Cardiovascular Research
|September 11, 2019
PubMed
Abstract

Insights

Endothelial microvesicles (MVs) disrupt vascular barrier function and activate neutrophils during inflammation. These MVs carry c-Src kinase, promoting endothelial cell dysfunction, but neutrophil activation is independent of c-Src.

Area of Science:

  • Cell Biology
  • Vascular Biology
  • Immunology

Background:

  • Microvesicles (MVs) mediate intercellular communication by transferring bioactive cargo.
  • Endothelial cells form the vascular barrier, crucial for regulating blood flow and tissue homeostasis.
  • Inflammation can compromise vascular integrity, leading to dysfunction.

Purpose of the Study:

  • To investigate the role of endothelial-derived microvesicles (EC-MVs) in vascular dysfunction during inflammation.
  • To determine the mechanisms by which EC-MVs impact endothelial barrier function and neutrophil activation.

Main Methods:

  • Quantified EC-MVs in mouse plasma after septic injury (cecal ligation and puncture).
  • Analyzed EC-MV production and cargo from cultured endothelial cells stimulated with inflammatory agents.
  • Assessed the functional effects of EC-MVs on endothelial cells and neutrophils in vitro.

Main Results:

  • Sepsis significantly increased plasma EC-MVs. Inflammatory agents induced diverse EC-MV production and cargo profiles.
  • EC-MVs triggered endothelial cell responses including myosin light chain phosphorylation, adherens junction dissociation, and increased albumin flux.
  • EC-MVs carrying c-Src kinase promoted endothelial barrier disruption; however, EC-MV-induced neutrophil activation and NETosis were c-Src-independent.

Conclusions:

  • Endothelial-derived microvesicles contribute to vascular dysfunction by impairing endothelial adherens junctions.
  • EC-MVs activate neutrophils, promoting endothelial inflammatory injury through mechanisms independent of c-Src kinase.
  • Signaling pathways involving c-Src kinase are critical for EC-MV-induced endothelial barrier disruption.
Keywords:
Barrier functionEndothelial cellsInflammationMicrovesiclesNeutrophils

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

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...
3.2K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.4K
Adherens Junctions01:24

Adherens Junctions

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
5.9K
Anchoring Junctions01:03

Anchoring Junctions

Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
4.6K
Tension Response at Adherens Junctions01:26

Tension Response at Adherens Junctions

The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
3.4K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.1K