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Published 25 October 2004. doi:10.1083/jcb.200404129
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 167, Number 2, 377-388
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Article

 A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them

Christopher V. Carman and Timothy A. Springer

The CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, MA 02115

Correspondence to Timothy A. Springer: springeroffice{at}cbr.med.harvard.edu

The basic route and mechanisms for leukocyte migration across the endothelium remain poorly defined. We provide definitive evidence for transcellular (i.e., through individual endothelial cells) diapedesis in vitro and demonstrate that virtually all, both para- and transcellular, diapedesis occurs in the context of a novel "cuplike" transmigratory structure. This endothelial structure was comprised of highly intercellular adhesion molecule-1– and vascular cell adhesion molecule-1–enriched vertical microvilli-like projections that surrounded transmigrating leukocytes and drove redistribution of their integrins into linear tracks oriented parallel to the direction of diapedesis. Disruption of projections was highly correlated with inhibition of transmigration. These findings suggest a novel mechanism, the "transmigratory cup", by which the endothelium provides directional guidance to leukocytes for extravasation.

Abbreviations used in this paper: BAPTA-AM, 1,2Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester); HUVEC, human umbilical vein endothelial cell; ICAM-1, intercellular adhesion molecule-1; IRM, interference reflection microscopy; LFA-1, leukocyte function-associated molecule-1; MCP-1, monocyte chemoattractant protein-1; PAF, platelet activating factor; PECAM-1, platelet/endothelial cell adhesion molecule-1; SDF-1, stromal cell–derived factor-1; TEM, transendothelial migration; VCAM-1, vascular cell adhesion molecule-1; VLA-4, very late antigen-4.


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