A feedback loop sustaining neutrophil extracellular trap formation involves S100 proteins, histones, TLR2 and RAGE, and is restrained by albumin - Takeaways - MDSpire

A feedback loop sustaining neutrophil extracellular trap formation involves S100 proteins, histones, TLR2 and RAGE, and is restrained by albumin

  • By

  • Vanessa de Carvalho Oliveira

  • Matthew Mazur

  • Patrick P. McDonald

  • June 1, 2026

  • 0 min

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  • 1

    Neutrophil extracellular trap (NET) formation is regulated by endogenous mediators, including S100 proteins and histones, which activate RAGE and TLR2.

  • 2

    Mass spectrometry identified seven S100 protein species and ten histone variants that bind to RAGE, promoting NET generation.

  • 3

    Antagonism of TLR2, but not TLR4, inhibits NET formation, indicating the specific role of TLR2 in mediating the effects of endogenous NET inducers.

  • 4

    Human serum albumin (HSA) limits NET formation by sequestering endogenous NET inducers, preventing their feedback on neutrophils.

  • 5

    Prior exposure to serum or albumin renders endogenous NET inducers ineffective, highlighting the physiological regulation of NET formation.

Original Source(s)

A feedback loop sustaining neutrophil extracellular trap formation involves S100 proteins, histones, TLR2 and RAGE, and is restrained by albumin

  • by Vanessa de Carvalho Oliveira, Matthew Mazur, Patrick P. McDonald

  • June 1, 2026

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