TY  - JOUR
AU  - Bader, Almke
AU  - Gao, Jincheng
AU  - Reiter, Nina
AU  - Siemes, Devon
AU  - Zehrer, Annette
AU  - Wei, Xiang
AU  - Hepper, Ingrid
AU  - de Vega Gómez, Enrique
AU  - Schmid, Bettina
AU  - Forné, Ignasi
AU  - Engel, Daniel Robert
AU  - Walzog, Barbara
AU  - Maier-Begandt, Daniela
TI  - SCAMP3 is essential for proper formation and function of neutrophil granules.
JO  - Journal of leukocyte biology
VL  - 117
IS  - 12
SN  - 0741-5400
CY  - Tokyo
PB  - Oxford University Press
M1  - DZNE-2025-01349
SP  - qiaf153
PY  - 2025
AB  - Host defense functions of neutrophils during infection critically depend on microbicidal and proteolytic proteins stored in primary, secondary, and tertiary granules that are released into the phagosome or into the extracellular space upon degranulation. Granules are generated during granulopoiesis, and impaired granule production or granule protein sorting has been linked to inefficient pathogen clearance resulting in recurrent bacterial and fungal infections. Here, we studied the role of secretory carrier associated membrane protein 3 (SCAMP3) for neutrophil defense functions. We generated Scamp3 knockout (KO) Hoxb8 cells and found that killing of Escherichia coli by Scamp3 KO Hoxb8 cell-derived neutrophils (dHoxb8 cells) was compromised as compared with control dHoxb8 cells in vitro. Mass spectrometric and Western blot analyses revealed a significant reduction of primary, secondary, and tertiary granule proteins in the genetic absence of Scamp3, resulting in a reduced overall granularity of these cells. Accordingly, degranulation was reduced in Scamp3 KO dHoxb8 cells compared with control dHoxb8 cells. Similarly, Scamp3 deficiency in zebrafish resulted in reduced neutrophil granularity in comparison with wild-type animals. However, neutrophil migration toward sites of E. coli infection was unaffected in scamp3 KO zebrafish larvae. In summary, SCAMP3 represents an important novel player in granule equipment and degranulation, with key functions in neutrophil defense mechanisms during host-pathogen interactions in vitro.
KW  - Animals
KW  - Neutrophils: immunology
KW  - Neutrophils: metabolism
KW  - Zebrafish
KW  - Cell Degranulation: immunology
KW  - Membrane Proteins: genetics
KW  - Membrane Proteins: immunology
KW  - Membrane Proteins: metabolism
KW  - Cytoplasmic Granules: metabolism
KW  - Cytoplasmic Granules: immunology
KW  - Escherichia coli: immunology
KW  - Escherichia coli Infections: immunology
KW  - Mice
KW  - Homeodomain Proteins: genetics
KW  - SCAMP3 (Other)
KW  - granules (Other)
KW  - host defense (Other)
KW  - infection (Other)
KW  - neutrophils (Other)
KW  - Membrane Proteins (NLM Chemicals)
KW  - Homeodomain Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41187789
DO  - DOI:10.1093/jleuko/qiaf153
UR  - https://pub.dzne.de/record/282589
ER  -