S100A8/A9 Is a Marker for the Release of Neutrophil Extracellular Traps and Induces Neutrophil Activation

Neutrophils are the most abundant innate immune cells in the circulation and they are the first cells recruited to sites of infection or inflammation. Almost half of the intracellular protein content in neutrophils consists of S100A8 and S100A9, though there has been controversy about their actual l...

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Published in:	Cells (Basel, Switzerland) Vol. 11; no. 2; p. 236
Main Authors:	Sprenkeler, Evelien G G, Zandstra, Judith, van Kleef, Nadine D, Goetschalckx, Ines, Verstegen, Bibian, Aarts, Cathelijn E M, Janssen, Hans, Tool, Anton T J, van Mierlo, Gerard, van Bruggen, Robin, Jongerius, Ilse, Kuijpers, Taco W
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 11-01-2022 MDPI
Subjects:	Acetic acid Antibodies Calgranulin A - metabolism Calgranulin B - metabolism calprotectin CD11b antigen Cell activation Cell Degranulation Chronic granulomatous disease Cytoplasm - metabolism Exocytosis Experiments Extracellular Traps - metabolism Flow cytometry Humans Inflammatory diseases Leukocytes (neutrophilic) Localization Microscopy MRP8/14 Neutrophil Activation neutrophil extracellular traps Neutrophils Neutrophils - metabolism Neutrophils - ultrastructure Phorbol 12-myristate 13-acetate Proteins Reagents S100A8/A9 Tumor necrosis factor-TNF Netherlands United Kingdom > UK United States > US Switzerland Germany S100A8/A9 neutrophil extracellular traps MRP8/14 neutrophils calprotectin
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Summary:	Neutrophils are the most abundant innate immune cells in the circulation and they are the first cells recruited to sites of infection or inflammation. Almost half of the intracellular protein content in neutrophils consists of S100A8 and S100A9, though there has been controversy about their actual localization. Once released extracellularly, these proteins are thought to act as damage-associated molecular patterns (DAMPs), though their mechanism of action is not well understood. These S100 proteins mainly form heterodimers (S100A8/A9, also known as calprotectin) and this heterocomplex is recognized as a useful biomarker for several inflammatory diseases. We observed that S100A8/A9 is highly present in the cytoplasmic fraction of neutrophils and is not part of the granule content. Furthermore, we found that S100A8/A9 was not released in parallel with granular content but upon the formation of neutrophil extracellular traps (NETs). Accordingly, neutrophils of patients with chronic granulomatous disease, who are deficient in phorbol 12-myristate 13-acetate (PMA)-induced NETosis, did not release S100A8/A9 upon PMA stimulation. Moreover, we purified S100A8/A9 from the cytoplasmic fraction of neutrophils and found that S100A8/A9 could induce neutrophil activation, including adhesion and CD11b upregulation, indicating that this DAMP might amplify neutrophil activation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2073-4409 2073-4409
DOI:	10.3390/cells11020236