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000282589 0247_ $$2doi$$a10.1093/jleuko/qiaf153
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000282589 0247_ $$2ISSN$$a1938-3673
000282589 037__ $$aDZNE-2025-01349
000282589 041__ $$aEnglish
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000282589 1001_ $$0P:(DE-2719)9001059$$aBader, Almke$$b0
000282589 245__ $$aSCAMP3 is essential for proper formation and function of neutrophil granules.
000282589 260__ $$aTokyo$$bOxford University Press$$c2025
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000282589 520__ $$aHost 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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000282589 650_7 $$2Other$$aSCAMP3
000282589 650_7 $$2Other$$agranules
000282589 650_7 $$2Other$$ahost defense
000282589 650_7 $$2Other$$ainfection
000282589 650_7 $$2Other$$aneutrophils
000282589 650_7 $$2NLM Chemicals$$aMembrane Proteins
000282589 650_7 $$2NLM Chemicals$$aHomeodomain Proteins
000282589 650_2 $$2MeSH$$aAnimals
000282589 650_2 $$2MeSH$$aNeutrophils: immunology
000282589 650_2 $$2MeSH$$aNeutrophils: metabolism
000282589 650_2 $$2MeSH$$aZebrafish
000282589 650_2 $$2MeSH$$aCell Degranulation: immunology
000282589 650_2 $$2MeSH$$aMembrane Proteins: genetics
000282589 650_2 $$2MeSH$$aMembrane Proteins: immunology
000282589 650_2 $$2MeSH$$aMembrane Proteins: metabolism
000282589 650_2 $$2MeSH$$aCytoplasmic Granules: metabolism
000282589 650_2 $$2MeSH$$aCytoplasmic Granules: immunology
000282589 650_2 $$2MeSH$$aEscherichia coli: immunology
000282589 650_2 $$2MeSH$$aEscherichia coli Infections: immunology
000282589 650_2 $$2MeSH$$aMice
000282589 650_2 $$2MeSH$$aHomeodomain Proteins: genetics
000282589 7001_ $$aGao, Jincheng$$b1
000282589 7001_ $$aReiter, Nina$$b2
000282589 7001_ $$aSiemes, Devon$$b3
000282589 7001_ $$aZehrer, Annette$$b4
000282589 7001_ $$aWei, Xiang$$b5
000282589 7001_ $$aHepper, Ingrid$$b6
000282589 7001_ $$ade Vega Gómez, Enrique$$b7
000282589 7001_ $$0P:(DE-2719)2241638$$aSchmid, Bettina$$b8$$udzne
000282589 7001_ $$aForné, Ignasi$$b9
000282589 7001_ $$aEngel, Daniel Robert$$b10
000282589 7001_ $$aWalzog, Barbara$$b11
000282589 7001_ $$00000-0001-8491-9820$$aMaier-Begandt, Daniela$$b12
000282589 773__ $$0PERI:(DE-600)2026833-6$$a10.1093/jleuko/qiaf153$$gVol. 117, no. 12, p. qiaf153$$n12$$pqiaf153$$tJournal of leukocyte biology$$v117$$x0741-5400$$y2025
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