Abstract
Nine polypeptide peaks with antibiotic activity were resolved from human polymorphonuclear leukocyte azurophil granule membranes. All but 1 of the 12 constituent polypeptides were identified by N-terminal sequence analysis. Near quantitative recovery of protein and activity permitted an assessment of the contribution of each species to the overall respiratory-burst-independent antimicrobial capacity of the cell. Three uncharacterized polypeptides were discovered, including two broad-spectrum antibiotics. One of these, a defensin that we have designated human neutrophil antimicrobial peptide 4, was more potent than previously described defensins but represented less than 1% of the total protein. The other, named azurocidin, was abundant and comparable to bactericidal permeability-increasing factor in its contribution to the killing of Escherichia coli.
MeSH Terms
Amino Acid Sequence
Anti-Bacterial Agents/blood,isolation & purification,pharmacology
Blood Proteins/isolation & purification
Candida albicans/drug effects
Chromatography, High Pressure Liquid
Enterococcus faecalis/drug effects
Escherichia coli/drug effects
Humans
Microbial Sensitivity Tests
Molecular Sequence Data
Molecular Weight
Neutrophils/analysis
Chemicals
Anti-Bacterial Agents
Blood Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Gabay J E
Beatrice and Samuel A. Seaver Laboratory, Department of Medicine, Cornell University Medical College, New York, NY 10021.
Scott R W
Campanelli D
Griffith J
Wilde C
Marra M N
Seeger M
Nathan C F
References (22)
22 references, click to expand
-
Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
Nature. 1970 Aug 15;227(5259):680-5
PMID: 5432063
-
Characterization of a protein from normal human polymorphonuclear leukocytes with bactericidal activity against Pseudomonas aeruginosa.
Infect Immun. 1986 Oct;54(1):142-8
PMID: 3093381
-
Antibacterial activity of cationic proteins from human granulocytes.
J Clin Invest. 1975 Nov;56(5):1118-24
PMID: 241758
-
Fungicidal properties of a chymotrypsin-like cationic protein from human neutrophils: adsorption to Candida parapsilosis.
Infect Immun. 1977 Aug;17(2):382-8
PMID: 19359
-
Purification and characterization of a potent bactericidal and membrane active protein from the granules of human polymorphonuclear leukocytes.
J Biol Chem. 1978 Apr 25;253(8):2664-72
PMID: 344320
-
Killing of gram-negative bacteria by polymorphonuclear leukocytes: role of an O2-independent bactericidal system.
J Clin Invest. 1982 Apr;69(4):959-70
PMID: 7042758
-
Cationic antimicrobial proteins isolated from human neutrophil granulocytes in the presence of diisopropyl fluorophosphate.
Infect Immun. 1984 Jul;45(1):29-35
PMID: 6376359
-
Nonoxidative antimicrobial reactions of leukocytes.
Contemp Top Immunobiol. 1984;14:283-343
PMID: 6380931
-
Subcellular location and properties of bactericidal factors from human neutrophils.
J Exp Med. 1986 Nov 1;164(5):1407-21
PMID: 3772295
-
Primary structure of human neutrophil elastase.
Proc Natl Acad Sci U S A. 1987 Apr;84(8):2228-32
PMID: 3550808
-
Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membranes.
J Biol Chem. 1987 Jul 25;262(21):10035-8
PMID: 3611052
-
Molecular cloning of human cathepsin G: structural similarity to mast cell and cytotoxic T lymphocyte proteinases.
Biochemistry. 1987 Apr 21;26(8):2289-93
PMID: 3304423
-
A 25-kDa NH2-terminal fragment carries all the antibacterial activities of the human neutrophil 60-kDa bactericidal/permeability-increasing protein.
J Biol Chem. 1987 Nov 5;262(31):14891-4
PMID: 3667613
-
Biochemical and amino acid sequence analysis of human eosinophil granule major basic protein.
J Biol Chem. 1988 Sep 5;263(25):12559-63
PMID: 3410852
-
Structure of a novel human granulocyte peptide with anti-ACTH activity.
Biochem Biophys Res Commun. 1988 Aug 30;155(1):524-9
PMID: 2843187
-
Isolation of a complementary DNA clone encoding a precursor to human eosinophil major basic protein.
J Exp Med. 1988 Dec 1;168(6):2295-308
PMID: 3199069
-
Nonoxidative fungicidal mechanisms of mammalian granulocytes: demonstration of components with candidacidal activity in human, rabbit, and guinea pig leukocytes.
Infect Immun. 1975 Jun;11(6):1226-34
PMID: 49298
-
Bactericidal activity of human lysozyme, muramidase-inactive lysozyme, and cationic polypeptides against Streptococcus sanguis and Streptococcus faecalis: inhibition by chitin oligosaccharides.
Infect Immun. 1985 Jun;48(3):720-8
PMID: 3922894
-
Oxygen-independent intracellular and oxygen-dependent extracellular killing of Escherichia coli S15 by human polymorphonuclear leukocytes.
J Clin Invest. 1985 Jul;76(1):206-12
PMID: 3894419
-
Defensins. Natural peptide antibiotics of human neutrophils.
J Clin Invest. 1985 Oct;76(4):1427-35
PMID: 2997278
-
Primary structures of three human neutrophil defensins.
J Clin Invest. 1985 Oct;76(4):1436-9
PMID: 4056036
-
Biochemical and functional similarities between human eosinophil-derived neurotoxin and eosinophil cationic protein: homology with ribonuclease.
Proc Natl Acad Sci U S A. 1986 May;83(10):3146-50
PMID: 3458170