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Epithelial permeability and the transepithelial migration of human neutrophils
Abstract:
Although polymorphonuclear leukocytes (PMN's) can migrate through every epithelium in the body regardless of its permeability, very little is known about the effect of epithelial permeability on PMN migration and the effect of emigrating PMN's on the permeability of the epithelium. In an in vitro model system of transepithelial migration, human PMN's were stimulated by 0.1 micrometer fMet-Leu-Phe to traverse confluent, polarized canine kidney epithelial monolayers of varying permeabilities. Epithelial permeability was determined by both conductance measurement and horseradish peroxidase (HRP) tracer studies. As epithelial permeability increased, the number of PMN invasion sites as well as the number of PMN's that traversed the monolayer increased. The effect of PMN migration on epithelial permeability was examined using the ultrastructural tracers HRP and lanthanum nitrate. PMN's traversing the monolayer made close cell-to-cell contacts with other invading PMNs and with adjacent epithelial cells. These close contacts appeared to prevent leakage of tracer across invasion sites. Following PMN emigration, epithelial junctional membranes reapproximated and were impermeable to the tracers. These results indicated that, in the absence of serum and connective tissue factors, (a) the number of PMN invasion sites and the number of PMN's that traversed an epithelium were a function of the conductance of the epithelium and (b) PMN's in the process of transepithelial migration maintained close cell-cell contacts and prevented the leakage of particles (greater than 5 nm in diameter) across the invasion site.
Insights
Epithelial permeability influences polymorphonuclear leukocyte (PMN) migration. PMNs migrating through epithelia maintain cell contacts, preventing leakage and preserving barrier integrity after emigration.
Area of Science:
- Cell Biology
- Immunology
- Epithelial Physiology
Background:
- Polymorphonuclear leukocytes (PMNs) are crucial for immune responses and can cross various epithelia.
- The interplay between epithelial permeability and PMN transepithelial migration is not well understood.
- Investigating how PMN migration affects epithelial barrier function is essential.
Purpose of the Study:
- To investigate the impact of epithelial permeability on PMN migration.
- To determine how emigrating PMNs influence epithelial permeability.
- To elucidate the mechanisms governing PMN transepithelial passage and its effect on epithelial integrity.
Main Methods:
- Utilized an in vitro model with confluent, polarized canine kidney epithelial monolayers.
- Stimulated human PMNs with fMet-Leu-Phe for transepithelial migration.
- Assessed epithelial permeability using conductance measurements and horseradish peroxidase (HRP) tracer studies.
- Examined the effect of PMN migration on permeability using ultrastructural tracers (HRP and lanthanum nitrate).
Main Results:
- Increased epithelial permeability correlated with a higher number of PMN invasion sites and transmigrated PMNs.
- PMNs maintained close cell-to-cell contacts during migration, preventing tracer leakage (>5 nm).
- Epithelial junctional membranes reapproximated post-emigration, restoring impermeability to tracers.
Conclusions:
- Epithelial conductance directly influences the number of PMN invasion sites and transmigration.
- During transepithelial migration, PMNs actively prevent particle leakage across invasion sites.
- PMN emigration, in this model, does not compromise long-term epithelial barrier function.