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Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611

CORRESPONDENCE William A. Muller: wamuller{at}northwestern.edu OR Zahra Mamdouh: z-mamdouh{at}northwestern.edu

Leukocyte migration across endothelial cell borders (paracellular) and through endothelial cells (transcellular) appear to be distinct processes. During paracellular migration, membrane from a parajunctional reticulum of interconnected vesicles, the endothelial lateral border recycling compartment (LBRC), moves to surround the leukocyte in a kinesin-mediated, microtubule-dependent manner. We show that transcellular migration likewise requires targeted trafficking of LBRC membrane. We show that in addition to platelet/endothelial cell adhesion molecule (PECAM; CD31), CD99 and junctional adhesion molecule A (JAM-A), but apparently not vascular endothelial cell–specific cadherin (cadherin 5, CD144), are components of the LBRC. During transcellular migration, LBRC membrane invests the transmigrating leukocyte. Intracellular adhesion molecule 1 (ICAM-1) on the apical endothelial surface is enriched around adherent leukocytes. Depolymerization of microtubules has no effect on ICAM-1 enrichment but blocks targeted trafficking of LBRC membrane and transcellular migration by >90%. Similar to their effects on paracellular transmigration, antibodies against PECAM or CD99, but not JAM-A, block transcellular migration. We conclude that similar molecular mechanisms promote both para- and transcellular migration.

Abbreviations used: DAB, 3,3'-diaminobenzidine; DCN, demecolcine; HRP, horseradish peroxidase; HUVEC, human umbilical vein endothelial cell; ICAM-1, intracellular adhesion molecule 1; immuno-EM, immunoelectron microscopy; JAM-A, junctional adhesion molecule A; LBRC, lateral border recycling compartment; MCP-1, monocyte chemotactic protein 1; PECAM, platelet/endothelial cell adhesion molecule; TEM, transendothelial migration; VE-cadherin, vascular endothelial cell–specific cadherin.

© 2009 Mamdouh et al.
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This article has been cited by other articles:

• Mamdouh, Z., Mikhailov, A., Muller, W. A. (2009). Transcellular migration of leukocytes is mediated by the endothelial lateral border recycling compartment. JCB 187: i7-i7 [Full Text]  

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