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Endothelial membrane reorganization during leukocyte extravasation

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Abstract

Leukocyte trafficking from the bloodstream to inflamed tissues across the endothelial barrier is an essential response in innate immunity. Leukocyte adhesion, locomotion, and diapedesis induce signaling in endothelial cells and this is accompanied by a profound reorganization of the endothelial cell surfaces that is only starting to be unveiled. Here we review the current knowledge on the leukocyte-mediated alterations of endothelial membrane dynamics and their role in promoting leukocyte extravasation. The formation of protein- and lipid-mediated cell adhesion nanodomains at the endothelial apical surface, the extension of micrometric apical membrane docking structures, which are derived from microvilli and embrace adhered leukocytes, as well as the vesicle-trafficking pathways that are required for efficient leukocyte diapedesis, are discussed. The coordination between these different endothelial membrane-remodeling events probably provides the road map for transmigrating leukocytes to find exit points in the vessel wall, in a context of severe mechanical and inflammatory stress. A better understanding of how vascular endothelial cells respond to immune cell adhesion should enable new therapeutic strategies to be developed that can abrogate uncontrolled leukocyte extravasation in inflammatory diseases.

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Abbreviations

PMN:

Polymorphonuclear

FCS:

Fluorescence correlation spectroscopy

TIRF:

Total internal reflection fluorescence

FRET:

Fluorescent resonance energy transfer

FRAP:

Fluorescence recovery after photobleaching

TEM:

Transendothelial migration

BBB:

Blood–brain barrier

LBR:

Lateral border recycling

DRM:

Detergent-resistant membranes

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Acknowledgments

We would like to thank M.A. Alonso, E. Cernuda-Morollón and S. Gharbi for critical reading of the manuscript. We also appreciate the help of F. Belio with the design of the figures. Dr. J. Millán is supported by grants SAF2008-01936, SAF2011-22624 from Ministerio de Ciencia e Innovación, Spain, and received research support from Biogen-Idec. B. Marcos-Ramiro is supported by an FPI fellowship from Ministerio de Ciencia e Innovación. N. Reglero-Real is supported by a JAE fellowship from CSIC.

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  1. Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, C/Nicolás Cabrera 1, Cantoblanco, 28049, Madrid, Spain

    Natalia Reglero-Real, Beatriz Marcos-Ramiro & Jaime Millán

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  1. Natalia Reglero-Real
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Correspondence to Jaime Millán.

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N. Reglero-Real and B. Marcos-Ramiro contributed equally to this work.

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Reglero-Real, N., Marcos-Ramiro, B. & Millán, J. Endothelial membrane reorganization during leukocyte extravasation. Cell. Mol. Life Sci. 69, 3079–3099 (2012). https://doi.org/10.1007/s00018-012-0987-4

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