Role of the endothelial surface layer in neutrophil recruitment

Alex Marki, Jeffrey D. Esko, Axel R. Pries, Klaus Ley

Research output: Contribution to journalReview articlepeer-review

98 Scopus citations

Abstract

Neutrophil recruitment in most tissues is limited to postcapillary venules, where E- and P-selectins are inducibly expressed by venular endothelial cells. These molecules support neutrophil rolling via binding of PSGL-1 and other ligands on neutrophils. Selectins extend #38 nm above the endothelial plasma membrane, and PSGL-1 extends to 50 nm above the neutrophil plasma membrane. However, endothelial cells are covered with an ESL composed of glycosaminoglycans that is $500 nm thick and has measurable resistance against compression. The neutrophil surface is also covered with a surface layer. These surface layers would be expected to completely shield adhesion molecules; thus, neutrophils should not be able to roll and adhere. However, in the cremaster muscle and in many other models investigated using intravital microscopy, neutrophils clearly roll, and their rolling is easily and quickly induced. This conundrum was thought to be resolved by the observation that the induction of selectins is accompanied by ESL shedding; however, ESL shedding only partially reduces the ESL thickness (to 200 nm) and thus is insufficient to expose adhesion molecules. In addition to its antiadhesive functions, the ESL also presents neutrophil arrest-inducing chemokines. ESL heparan sulfate can also bind L-selectin expressed by the neutrophils, which contributes to rolling and arrest. We conclude that ESL has both proadhesive and antiadhesive functions. However, most previous studies considered either only the proadhesive or only the antiadhesive effects of the ESL. An integrated model for the role of the ESL in neutrophil rolling, arrest, and transmigration is needed.

Original languageEnglish (US)
Pages (from-to)503-515
Number of pages13
JournalJournal of Leukocyte Biology
Volume98
Issue number4
DOIs
StatePublished - Oct 2015
Externally publishedYes

Keywords

  • Cell adhesion
  • Emigration
  • Endothelial glycocalyx
  • Proteoglycans

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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