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024 7 _ |a 10.1093/jleuko/qiaf153
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024 7 _ |a 0741-5400
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024 7 _ |a 1938-3673
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037 _ _ |a DZNE-2025-01349
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Bader, Almke
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245 _ _ |a SCAMP3 is essential for proper formation and function of neutrophil granules.
260 _ _ |a Tokyo
|c 2025
|b Oxford University Press
336 7 _ |a article
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520 _ _ |a 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.
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650 _ 7 |a SCAMP3
|2 Other
650 _ 7 |a granules
|2 Other
650 _ 7 |a host defense
|2 Other
650 _ 7 |a infection
|2 Other
650 _ 7 |a neutrophils
|2 Other
650 _ 7 |a Membrane Proteins
|2 NLM Chemicals
650 _ 7 |a Homeodomain Proteins
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Neutrophils: immunology
|2 MeSH
650 _ 2 |a Neutrophils: metabolism
|2 MeSH
650 _ 2 |a Zebrafish
|2 MeSH
650 _ 2 |a Cell Degranulation: immunology
|2 MeSH
650 _ 2 |a Membrane Proteins: genetics
|2 MeSH
650 _ 2 |a Membrane Proteins: immunology
|2 MeSH
650 _ 2 |a Membrane Proteins: metabolism
|2 MeSH
650 _ 2 |a Cytoplasmic Granules: metabolism
|2 MeSH
650 _ 2 |a Cytoplasmic Granules: immunology
|2 MeSH
650 _ 2 |a Escherichia coli: immunology
|2 MeSH
650 _ 2 |a Escherichia coli Infections: immunology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Homeodomain Proteins: genetics
|2 MeSH
700 1 _ |a Gao, Jincheng
|b 1
700 1 _ |a Reiter, Nina
|b 2
700 1 _ |a Siemes, Devon
|b 3
700 1 _ |a Zehrer, Annette
|b 4
700 1 _ |a Wei, Xiang
|b 5
700 1 _ |a Hepper, Ingrid
|b 6
700 1 _ |a de Vega Gómez, Enrique
|b 7
700 1 _ |a Schmid, Bettina
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700 1 _ |a Forné, Ignasi
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700 1 _ |a Engel, Daniel Robert
|b 10
700 1 _ |a Walzog, Barbara
|b 11
700 1 _ |a Maier-Begandt, Daniela
|0 0000-0001-8491-9820
|b 12
773 _ _ |a 10.1093/jleuko/qiaf153
|g Vol. 117, no. 12, p. qiaf153
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|t Journal of leukocyte biology
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|y 2025
|x 0741-5400
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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