Abstract
The basic route and mechanism for diapedesis has not yet to be fully defined. Here we present evidence that "cell-cell separation" between endothelial cells (ECs) may provide a route for leukocyte diapedesis. We unexpectedly found that extensive interaction between peripheral blood leukocytes and ECs that were activated by TNF-alpha induced the opening of EC contacts and, surprisingly, resulted in cell-cell separation. This event was specific to the intercellular adhesion molecules-1 (ICAM-1)/leukocyte function- associated antigen-1 interaction, as demonstrated by the following: (1) ICAM-1 expression correlated with increased EC contraction; and (2) the blocking of ICAM-1 selectively inhibited EC separation. Thus, we suggest that "cell-cell separation" could be a mechanism for diapedesis in situations that may require massive leukocyte infiltration.
Highlights
Leukocyte extravasation is a critical event in immune surveillance (Springer, 1994)
Crossing endothelial barriers is required for leukocyte trafficking and immune surveillance
By using a simplified in vitro model to monitor endothelial behavior under either static or flow conditions, we unexpectedly found that enhanced endothelial contraction stimulated by leukocyte binding results in "cell-cell separation"
Summary
Leukocyte extravasation is a critical event in immune surveillance (Springer, 1994) This phenomenon occurs by migration of leukocytes either directly through individual microvascular endothelial cells (ECs) (transcellular route) or between them, at interendothelial cell junctions (papacelluar route) (Greenwood et al, 1994; Feng et al, 1998). In both cases, the process is characterized by sequential events: arrest from rolling mediated by selectin, integrin-dependent firm adhesion, and transmigration across the endothelium (Springer, 1994). Previous studies have only provided a limited explanation of this rapid and excessive transmigration
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