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Updated: May 24, 2026

Neutrophil Lifespan Extension with CLON-G and an In Vitro Spontaneous Death Assay
Published on: May 12, 2023
Constitutive neutrophil apoptosis: regulation by cell concentration via S100 A8/9 and the MEK-ERK pathway
Mizhir Atallah1, Alon Krispin, Uriel Trahtemberg
1The Laboratory for Cellular and Molecular Immunology, Department of Medicine, Hadassah-Hebrew University Medical Center Jerusalem, Jerusalem, Israel.
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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