PMID:2997278

Citation	Ganz, T, Selsted, ME, Szklarek, D, Harwig, SS, Daher, K, Bainton, DF and Lehrer, RI (1985) Defensins. Natural peptide antibiotics of human neutrophils. J. Clin. Invest. 76:1427-35
Abstract	We extracted a granule-rich sediment from normal human neutrophils and subjected it to chromatographic, electrophoretic, and functional analysis. The extract contained three small (molecular weight less than 3,500) antibiotic peptides that were named human neutrophil peptide (HNP)-1, HNP-2, and HNP-3, and which will be referred to as "defensins." HNP 1-3, a mixture of the three defensins, killed Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli effectively in vitro when tested in 10 mM phosphate buffer containing certain nutrients, but it had little or no bactericidal activity in nutrient-free buffer. In contrast, the nutrient-free buffer supported a high degree of activity by HNP 1-3 against Cryptococcus neoformans. In addition to its antibacterial and antifungal properties, HNP 1-3 directly inactivated herpes simplex virus, Type 1. Two of the individual purified defensins, HNP-1 and HNP-2, were as microbicidal as the mixture HNP 1-3. HNP-3 was less active than the other defensins against most but not all of the microbes tested. Immunoperoxidase stains revealed HNP 1-3 to have a granular localization in the neutrophil's cytoplasm by light microscopy. Frozen thin section immunogold transmission electron microscopy showed HNP 1-3 to be localized in azurophil granules. These studies define a broad-spectrum antimicrobial system in human neutrophils. The defensin system may operate in conjunction with or independently from oxygen-dependent microbicidal processes to enable human neutrophils to inactivate and destroy potential pathogens.
Links	PubMed PMC424093 Online version:10.1172/JCI112120
Keywords	Amino Acids/analysis; Bacteria/drug effects; Blood Proteins/isolation & purification; Blood Proteins/pharmacology; Blood Proteins/physiology; Chromatography; Cryptococcus neoformans/drug effects; Cytoplasmic Granules/analysis; Electrophoresis, Polyacrylamide Gel; Humans; Microbial Sensitivity Tests; Neutrophils/analysis; Neutrophils/physiology; Simplexvirus/drug effects; alpha-Defensins
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:DEF1		GO:0042581: specific granule	ECO:0000314:		C		Methods (purification of HNP)	complete
HUMAN:DEF1		GO:0001909: leukocyte mediated cytotoxicity	ECO:0000314:		P		Table III and Methods (purification of HNP) indicate HNP found in leukocyte, cytotoxicity from killing of bacterial, fungal, viral targets	complete
HUMAN:DEF1		GO:0051607: defense response to virus	ECO:0000314:		P		Table III	complete
HUMAN:DEF1		GO:0042742: defense response to bacterium	ECO:0000314:		P		Table III shows bacterial decrease (death) after exposure to the HPN1-3 individually and together.	complete
HUMAN:DEF1		GO:0050832: defense response to fungus	ECO:0000314:		P		Table III	complete
HUMAN:DEF3		GO:0042581:	ECO:0000314:				Methods (purification of HNP)	complete
HUMAN:DEF3		GO:0050832: defense response to fungus	ECO:0000314:		P		Table III	complete
HUMAN:DEF3		GO:0051607: defense response to virus	ECO:0000314:		P		Table III	complete
HUMAN:DEF3		GO:0042742: defense response to bacterium	ECO:0000314:		P		Table III	complete
HUMAN:DEF3		GO:0001909: leukocyte mediated cytotoxicity	ECO:0000314:		P		Table III and Methods (purification of HNP) shows HNP found in leukocytes, cytotoxicity implied from killing of target cells/virus	complete

References

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