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Constitutive Neutrophil Apoptosis: Regulation by Cell Concentration via S100 A8/9 and the MEK – ERK Pathway

Authors
Journal
PLoS ONE
1932-6203
Publisher
Public Library of Science
Publication Date
Volume
7
Issue
2
Identifiers
DOI: 10.1371/journal.pone.0029333
Keywords
  • Research Article
  • Biology
  • Anatomy And Physiology
  • Immune Physiology
  • Physiological Processes
  • Biochemistry
  • Proteins
  • Immunology
  • Immunity
  • Molecular Cell Biology
  • Cellular Types
  • Signal Transduction
  • Signaling Cascades
  • Signaling In Cellular Processes
  • Proteomics
  • Medicine
  • Clinical Immunology
Disciplines
  • Biology

Abstract

Programmed cell death (PCD) is a fundamental mechanism in tissue and cell homeostasis. It was long suggested that apoptosis regulates the cell number in diverse cell populations; however no clear mechanism was shown. Neutrophils are the short-lived, first-line defense of innate immunity, with an estimated t = 1/2 of 8 hours and a high turnover rate. Here we first show that spontaneous neutrophil constitutive PCD is regulated by cell concentrations. Using a proteomic approach, we identified the S100 A8/9 complex, which constitutes roughly 40% of cytosolic protein in neutrophils, as mediating this effect. We further demonstrate that it regulates cell survival via a signaling mechanism involving MEK-ERK via TLR4 and CD11B/CD18. This mechanism is suggested to have a fine-tuning role in regulating the neutrophil number in bone marrow, peripheral blood, and inflammatory sites.

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