Interleukin-1beta reduces transcellular monocyte diapedesis and compromises endothelial adherens junction integrity.
OBJECTIVE
Diapedesis occurs through endothelial cell-cell junctions (paracellular) or through individual endothelial cells without disrupting junctions (transcellular). While in vitro studies have provided considerable insight into mechanisms controlling paracellular diapedesis, little is known about what regulates transcellular diapedesis. The authors investigated whether transcellular diapedesis is susceptible to IL-1beta exposure of the endothelium.


METHODS
Laser scanning confocal microscopy and biochemical analysis were used to determine the effect of IL-1beta pretreatment of the endothelium on adherens junctional morphology and monocyte transcellular diapedesis in cocultures of human peripheral blood monocytes and coronary artery endothelial cells.


RESULTS
IL-1beta pretreatment caused a 40% decrease in the number of migrating monocytes that used a transcellular route of diapedesis, and resulted in elongate endothelial cell morphology, a reorganization of the F-actin cytoskeleton, and a significant decrease in transendothelial electrical resistance. In IL-1beta treated monolayers, VE-cadherin and its associated catenins were distributed in a punctate pattern in comparison to the lacy pattern seen in control monolayers. Coimmunoprecipitation of VE-cadherin molecular assemblies revealed that IL-1beta-mediated changes in distribution were associated with a decrease in the presence of cadherin/catenin complexes in the detergent insoluble fraction.


CONCLUSIONS
IL-1beta-induced rearrangement of interendothelial adherens junctions facilitates paracellular diapedesis at the expense of transcellular diapedesis.
Ferreira
Alexander M
AM
Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario, Canada.
McNeil
Ceara J
CJ
Stallaert
Karen M
KM
Rogers
Kem A
KA
Sandig
Martin
M
D022005:Adherens Junctions / Q000187:drug effects / Q000502:physiology*; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D051177:Catenins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D051177:Catenins; D007375:Interleukin-1; D000099152:Cadherin 5