title: Serglycin participates in retention of α-defensin in granules during myelopoiesis.
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.
authors.affiliation: The Granulocyte Research Laboratory, Department of Hematology, National University Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Glenthøj
authors.forename: Jack B
authors.initials: JB
authors.lastname: Cowland
authors.forename: Niels H
authors.initials: NH
authors.lastname: Heegaard
authors.forename: Maria T
authors.initials: MT
authors.lastname: Larsen
authors.forename: Niels
authors.initials: N
authors.lastname: Borregaard
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D042381:Granulocyte Precursor Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000378:metabolism; D038042:Myelopoiesis; D021381:Protein Transport; D011509:Proteoglycans / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D023084:alpha-Defensins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D011509:Proteoglycans; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C075430:serglycin