Cytosolic S100A8/A9 promotes Ca²⁺ supply at LFA-1 adhesion clusters during neutrophil recruitment.

ABSTRACT: S100A8/A9 is an endogenous alarmin secreted by myeloid cells during many acute and chronic inflammatory disorders. Despite increasing evidence of the proinflammatory effects of extracellular S100A8/A9, little is known about its intracellular function. Here, we show that cytosolic S100A8/A9 is indispensable for neutrophil post-arrest modifications during outside-in signaling under flow conditions in vitro and neutrophil recruitment in vivo, independent of its extracellular functions. Mechanistically, genetic deletion of S100A9 in mice caused dysregulated Ca²⁺ signatures in activated neutrophils resulting in reduced Ca²⁺ availability at the formed LFA-1/F-actin clusters with defective β₂ integrin outside-in signaling during post-arrest modifications. Conseque

SUBMITTER: Napoli M 

PROVIDER: S-EPMC11658764 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature