Defensin-rich granules of human neutrophils: characterization of secretory properties

The various granule subtypes of the human neutrophil differ in propensity for exocytosis. As a rule, granules formed at late stages of myelopoiesis have a higher secretory potential than granules formed in more immature myeloid cells. Neutrophils contain four closely related α-defensins, which are s...

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Published in:Biochimica et biophysica acta 2002-08, Vol.1591 (1), p.29-35
Main Authors: Faurschou, Mikkel, Sørensen, Ole E, Johnsen, Anders H, Askaa, Jon, Borregaard, Niels
Format: Article
Language:English
Subjects:
Antibodies
Cytochalasin B - pharmacology
Defensin
Defensins - immunology
Defensins - metabolism
ELISA
Enzyme-Linked Immunosorbent Assay - methods
Exocytosis
Humans
In Vitro Techniques
Ionomycin - pharmacology
Ionophores - pharmacology
Neutrophils - drug effects
Neutrophils - metabolism
Peroxidase-positive granule
Reproducibility of Results
Subcellular fractionation
Subcellular Fractions
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Summary:The various granule subtypes of the human neutrophil differ in propensity for exocytosis. As a rule, granules formed at late stages of myelopoiesis have a higher secretory potential than granules formed in more immature myeloid cells. Neutrophils contain four closely related α-defensins, which are stored in a subset of azurophil granules. These defensin-rich azurophil granules (DRG) are formed later than defensin-poor azurophil granules, near the promyelocyte/myelocyte transition. In order to characterize the secretory properties of DRG, we developed a sensitive and accurate ELISA for detection of the neutrophil α-defensins HNP 1–3. This allowed us to quantify the exocytosis of α-defensins and markers of azurophil (myeloperoxidase), specific (lactoferrin) and gelatinase (gelatinase) granules from neutrophils stimulated with different secretagogues. The release pattern of α-defensins correlated perfectly with the release of myeloperoxidase and showed no resemblance to the exocytosis of lactoferrin or gelatinase. This finding was substantiated through subcellular fractionation experiments. In conclusion, despite a distinct profile of biosynthesis, DRG are indistinguishable from defensin-poor azurophil granules with respect to exocytosis. Thus, in contrast to peroxidase-negative granules, azurophil granules display homogeneity in their availability for extracellular release.
ISSN:0167-4889
0006-3002
1879-2596
DOI:10.1016/S0167-4889(02)00243-4