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Interleukin‐1β Reduces Transcellular Monocyte Diapedesis and Compromises Endothelial Adherens Junction Integrity
Author(s) -
FERREIRA ALEXANDER M.,
MCNEIL CEARA J.,
STALLAERT KAREN M.,
ROGERS KEM A.,
SANDIG MARTIN
Publication year - 2005
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680500253493
Subject(s) - adherens junction , transcellular , paracellular transport , microbiology and biotechnology , tight junction , cell junction , endothelium , endothelial stem cell , biology , chemistry , biophysics , cadherin , in vitro , cell , biochemistry , endocrinology , membrane , permeability (electromagnetism)
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‐1β exposure of the endothelium. Methods: Laser scanning confocal microscopy and biochemical analysis were used to determine the effect of IL‐1β 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‐1β 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‐1β 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‐1β‐mediated changes in distribution were associated with a decrease in the presence of cadherin/catenin complexes in the detergent insoluble fraction. Conclusions: IL‐1β‐induced rearrangement of interendothelial adherens junctions facilitates paracellular diapedesis at the expense of transcellular diapedesis.