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Kinetics of leukocyte-induced changes in endothelial barrier function
N Gautam1, P Hedqvist, L Lindbom
1Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden.
British Journal of Pharmacology
|December 10, 1998
Summary
Polymorphonuclear leukocytes (PMN) adhesion to endothelial cells (EC) rapidly disrupts the endothelial barrier, increasing plasma leakage during inflammation. This study reveals PMN adhesion, not just transmigration, directly impacts EC junctional integrity.
Area of Science:
- Immunology
- Cell Biology
- Vascular Biology
Background:
- Polymorphonuclear leukocytes (PMN) extravasation and plasma leakage are critical inflammatory events.
- Understanding endothelial barrier function changes during inflammation is crucial for therapeutic development.
Purpose of the Study:
- To investigate the kinetics of PMN-induced changes in endothelial barrier function.
- To analyze the direct effects of PMN adhesion on endothelial cell (EC) integrity.
Main Methods:
- Utilized a two-compartment diffusion chamber model with confluent EC monolayers.
- Continuously measured transendothelial electrical resistance (TEER) and protein efflux.
- Analyzed PMN migration and adhesion using chemotactic stimulation (fMLP, LTB4) and anti-CD18 mAb.
Main Results:
- Chemotactic stimulation induced a prompt decline in TEER, increased protein flux, and PMN transmigration.
- PMN adhesion alone, without transmigration, caused a fall in TEER and increased protein permeability.
- PMN adhesion triggered a rapid rise in endothelial cell cytosolic free Ca2+, indicating an active EC response.
Conclusions:
- Activated PMN directly impact EC junctional integrity through adhesion-dependent events.
- The in vitro model allows sensitive analysis of leukocyte activation effects on EC barrier function.
- Endothelial barrier disruption is linked to PMN adhesion, independent of transmigration.