Related Experiment Videos
Endothelial cell heterogeneity in venules of mouse airways induced by polarized inflammatory stimulus
T J Murphy1, G Thurston, T Ezaki
1Department of Anatomy and Cardiovascular Research Institute,* University of California, San Francisco, California, USA.
Abstract:
We sought to determine whether the changes in microvascular endothelial cells (EC) caused by a polarized chronic inflammatory stimulus depend on proximity to the stimulus. C3H mice were infected with Mycoplasma pulmonis, which attaches to the airway epithelium and creates a polarized inflammatory stimulus across the airway wall. At 1, 2, or 4 weeks, the tracheal vasculature was stained by perfusion of silver nitrate to mark EC borders or biotinylated Lycopersicon esculentum lectin to label the EC surface and adherent leukocytes. E-selectin immunoreactivity and EC proliferation were also localized. We found that the size, shape, and immunoreactivity for adhesion molecules on EC nearest the airway lumen (subepithelial EC) were different from those on the opposite surface of the same vessels. Subepithelial EC were smaller, more irregular in shape, had greater E-selectin immunoreactivity, and had twice as many adherent leukocytes. In contrast, proliferating EC were uniformly distributed around the vessel circumference. We conclude that the polarized stimulus created by M. pulmonis infection differentially changes the size, shape, and function of EC nearest the airway epithelium. This heterogeneity may result from a gradient of inflammatory mediators that triggers the influx of leukocytes into the airway lumen.
Insights
Inflammation from Mycoplasma pulmonis infection alters airway endothelial cells (EC). EC nearest the airway lumen show distinct changes, suggesting a gradient of inflammatory mediators.
Area of Science:
- Immunology
- Cell Biology
- Respiratory Medicine
Background:
- Chronic inflammation in airways can affect microvascular endothelial cells (EC).
- Mycoplasma pulmonis infection in mice creates a polarized inflammatory stimulus across the airway wall.
Purpose of the Study:
- To investigate if changes in microvascular EC due to polarized inflammation depend on their proximity to the stimulus.
- To characterize the alterations in EC size, shape, and function in response to airway inflammation.
Main Methods:
- C3H mice infected with Mycoplasma pulmonis.
- Tracheal vasculature stained using silver nitrate and biotinylated Lycopersicon esculentum lectin.
- Localization of E-selectin immunoreactivity and EC proliferation.
Main Results:
- Endothelial cells (EC) nearest the airway lumen (subepithelial EC) exhibited smaller size, irregular shape, and greater E-selectin immunoreactivity compared to EC on the opposite surface.
- Subepithelial EC had twice the number of adherent leukocytes.
- EC proliferation was uniformly distributed around the vessel circumference.
Conclusions:
- A polarized inflammatory stimulus, such as Mycoplasma pulmonis infection, differentially affects EC size, shape, and function based on their location relative to the airway epithelium.
- This heterogeneity in EC response may be mediated by a gradient of inflammatory mediators, influencing leukocyte influx.