Identification of a phenotypically and functionally distinct population of long-lived neutrophils in a model of reverse endothelial migration

Christopher D. Buckley, Ewan A. Ross, Helen M. McGettrick, Chloe E. Osborne, Oliver Haworth, Caroline Schmutz, Philip C.W. Stone, Mike Salmon, Nick M. Matharu, Rajiv K. Vohra, Gerard B. Nash, G. Ed Rainger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Recent studies have demonstrated that neutrophils are not a homogenous population of cells. Here, we have identified a subset of human neutrophils with a distinct profile of cell-surface receptors [CD54high, CXC chemokine receptor 1low (CXCR1low)], which represent cells that have migrated through an endothelial monolayer and then re-emerged by reverse transmigration (RT). RT neutrophils, when in contact with endothelium, were rescued from apoptosis, demonstrate functional priming, and were rheologically distinct from neutrophils that had not undergone transendothelial migration. In vivo, 1-2% of peripheral blood neutrophils in patients with systemic inflammation exhibit a RT phenotype. A smaller population existed in healthy donors (≈0.25%). RT neutrophils were distinct from naïve circulatory neutrophils (CD54low, CXCR1high) and naïve cells after activation with formyl-Met-Leu-Phe (CD54low, CXCR1low). It is important that the RT phenotype (CD54 high, CXCR1low) is also distinct from tissue-resident neutrophils (CD54low, CXCR1low). Our results demonstrate that neutrophils can migrate in a retrograde direction across endothelial cells and suggest that a population of tissue-experienced neutrophils with a distinct phenotype and function are present in the peripheral circulation in humans in vivo.

Original languageEnglish
Pages (from-to)303-311
Number of pages9
JournalJournal of Leukocyte Biology
Volume79
Issue number2
DOIs
Publication statusPublished - 1 Feb 2006

Keywords

  • Chronic inflammation
  • Migration
  • Recirculation

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