Cellular and Molecular Life Sciences

, Volume 74, Issue 10, pp 1871–1881

Reverse transendothelial cell migration in inflammation: to help or to hinder?


DOI: 10.1007/s00018-016-2444-2

Cite this article as:
Burn, T. & Alvarez, J.I. Cell. Mol. Life Sci. (2017) 74: 1871. doi:10.1007/s00018-016-2444-2


The endothelium provides a strong barrier separating circulating blood from tissue. It also provides a significant challenge for immune cells in the bloodstream to access potential sites of infection. To mount an effective immune response, leukocytes traverse the endothelial layer in a process known as transendothelial migration. Decades of work have allowed dissection of the mechanisms through which immune cells gain access into peripheral tissues, and subsequently to inflammatory foci. However, an often under-appreciated or potentially ignored question is whether transmigrated leukocytes can leave these inflammatory sites, and perhaps even return across the endothelium and re-enter circulation. Although evidence has existed to support “reverse” transendothelial migration for a number of years, it is only recently that mechanisms associated with this process have been described. Here we review the evidence that supports both reverse transendothelial migration and reverse interstitial migration within tissues, with particular emphasis on some of the more recent studies that finally hint at potential mechanisms. Additionally, we postulate the biological significance of retrograde migration, and whether it serves as an additional mechanism to limit pathology, or provides a basis for the dissemination of systemic inflammation.


Reverse migration rTEM Reverse interstitial migration Intravasation Transmigration Endothelial cell Neutrophil T cell Monocyte 

Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  1. 1.Institute of Immunology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Pathobiology, School of Veterinary MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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