Roles of neutrophils in the regulation of the extent of human inflammation through delivery of IL-1 and clearance of chemokines

Alexander Basran, Maisha Jabeen, Lynne Bingle, Clare A. Stokes, David Dockrell, Moira K. B. Whyte, Sarah R. Walmsley, Kathryn R. Higgins, Stefanie N. Vogel, Heather L. Wilson, Lynne R. Prince, Elizabeth C. Prestwich, Ruth A. Sabroe, Lisa C. Parker, Ian Sabroe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

This study examined the establishment of neutrophilic inflammation in humans. We tested the hypotheses that neutrophil recruitment was associated with local CXCL8 production and that neutrophils themselves might contribute to the regulation of the size of the inflammatory response. Humans were challenged i.d. with endotoxin. Biopsies of these sites were examined for cytokine production and leukocyte recruitment by qPCR and IHC. Additional in vitro models of inflammation examined the ability of neutrophils to produce and sequester cytokines relevant to neutrophilic inflammation. i.d. challenge with 15 ng of a TLR4-selective endotoxin caused a local inflammatory response, in which 1% of the total biopsy area stained positive for neutrophils at 6 h, correlating with 100-fold up-regulation in local CXCL8 mRNA generation. Neutrophils themselves were the major source of the early cytokine IL-1 beta. In vitro, neutrophils mediated CXCL8 but not IL-1 beta clearance (>90% clearance of

Original languageEnglish
Pages (from-to)7-19
Number of pages13
JournalJournal of Leukocyte Biology
Volume93
Issue number1
DOIs
Publication statusPublished - Jan 2013

Keywords

  • Toll-like receptor
  • endotoxin
  • neutrophil elastase
  • Interleukin-8
  • intradermal
  • NECROSIS-FACTOR-ALPHA
  • HUMAN POLYMORPHONUCLEAR LEUKOCYTES
  • RESPIRATORY-DISTRESS-SYNDROME
  • TOLL-LIKE RECEPTOR-2
  • IN-VIVO
  • CROSS-DESENSITIZATION
  • LUNG-DISEASE
  • ACTIVATION
  • EXPRESSION
  • CXCR1

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