Openings through endothelial cells associated with increased microvascular permeability.

Area of Science:

• Vascular biology
• Cell biology
• Physiology

Background:

• Microvascular permeability is crucial for regulating fluid and solute exchange.
• Increased permeability is associated with openings in the microvascular endothelium, primarily in venules.
• The exact mechanisms and pathways of these openings are not fully understood.

Purpose of the Study:

• To investigate the structural characteristics and formation pathways of openings in microvascular endothelium.
• To determine if openings form between endothelial cells or through the cells themselves.
• To explore the role of mediators and cellular structures in the development of these openings.

Main Methods:

• Reconstruction of endothelial openings using electron microscopy of serial sections.
• Analysis of endothelial cell morphology and intercellular junctions.
• Induction of permeability changes using specific agents like ionophore A23187 and vascular endothelial growth factor (VEGF), and high transmural pressures.

Main Results:

• Openings were found to frequently pass through the periphery of endothelial cells, near intact intercellular junctions.
• Transcellular pathways were identified as the principal type of opening induced by A23187, VEGF, and high pressures.
• Evidence suggests that vacuolar channels may fuse with both luminal and abluminal surfaces, potentially forming these transcellular openings.

Conclusions:

• Transcellular pathways represent a significant mechanism for increased microvascular permeability.
• The formation of these pathways may involve the fusion of intracellular vacuoles with the cell surface.
• Understanding these pathways provides insight into endothelial barrier function and regulation.