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Blood. 2011 Oct 20;118(16):4440-8. doi: 10.1182/blood-2011-06-362947. Epub 2011 Aug 17.

Serglycin participates in retention of α-defensin in granules during myelopoiesis.

Author information

1
The Granulocyte Research Laboratory, Department of Hematology, National University Hospital, University of Copenhagen, Copenhagen, Denmark.

Abstract

The mechanism by which proteins are targeted to neutrophil granules is largely unknown. The intracellular proteoglycan serglycin has been shown to have important functions related to storage of proteins in several types of granules. The possible role of serglycin in the localization of the α-defensin, human neutrophil peptide 1 (HNP-1), a major azurophil granule protein in human neutrophils, was investigated. Murine myeloid cells, stably transfected to express HNP-1, were capable of processing HNP-1, and HNP-1 was found to associate with serglycin in murine and human myeloid cell lines as well as in human bone marow cells. A transgenic mouse expressing HNP-1 in the myeloid compartment was crossed with mice deficient in serglycin or neutrophil elastase to investigate HNP-1 sorting and processing. Neither deficiency affected processing of HNP-1, but the ability to retain fully processed HNP-1 intracellularly was reduced in mice that lack serglycin. Human granulocyte precursors transfected with siRNA against serglycin displayed similar reduced capability to retain fully processed HNP-1, demonstrating a role of serglycin in retaining mature HNP-1 intracellularly, thus preventing potential toxic effects of extracellular HNP-1.

PMID:
21849484
DOI:
10.1182/blood-2011-06-362947
[Indexed for MEDLINE]
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