Two 29-kD polypeptides, azurocidin and p29b, were purified to homogeneity from human neutrophils by acid extraction of azurophil granule membrane-associated material followed by gel filtration and reverse-phase chromatography. Azurocidin and p29b share NH2-terminal sequence homology with each other as well as with elastase, cathepsin G, and other serine proteases. p29b bound [3H]diisopropyl fluorophosphate and hydrolyzed elastin, casein, and hemoglobin. A peptide substrate for p29b could not be identified. Azurocidin neither bound [3H]diisopropyl fluorophosphate nor hydrolyzed any of the proteins, peptides, or esters tested. In microbicidal assays, purified azurocidin was comparable to p29b in activity against Escherichia coli, Streptococcus faecalis, and Candida albicans. The antimicrobial activity of azurocidin was enhanced under mildly acidic conditions, but was inhibited in a dose-dependent manner by NaCl, CaCl2, or serum. Immunoblot analysis with monospecific antibodies localized greater than 90% of the azurocidin and greater than 75% of the p29b to azurophil granule-rich fractions of PMN lysates. Immunoelectron microscopy confirmed the localization of azurocidin to the azurophil granules. Azurocidin associated with the azurophil granule membrane, but did not appear to be an integral membrane protein. Thus, azurocidin and p29b are members of a family of serine protease homologs stored in azurophil granules and may play a role in inflammatory and antimicrobial processes involving PMN.
D Campanelli, P A Detmers, C F Nathan, J E Gabay
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Monoclonal Antibody AP-282 Recognizes a Marker for Human Polymorphonuclear Granules
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Hybridoma | 1992 |
Substrate and inhibitor studies on proteinase 3
CM Kam, JE Kerrigan, KM Dolman, R Goldschmeding, AE von Borne, JC Powers |
FEBS Letters | 1992 |
Treatment of patients with chronic granulomatous disease with recombinant human interferon-gamma does not improve neutrophil oxidative metabolism, cytochrome b558 content or levels of four anti-microbial proteins
TJ Mühlebach, J Gabay, C Nathan, C Erny, G Dopfer, H Schroten, V Wahn, RA Seger |
Clinical & Experimental Immunology | 1992 |
Agents that increase the permeability of the outer membrane
M Vaara |
Microbiological reviews | 1992 |
Three human elastase-like genes coordinately expressed in the myelomonocyte lineage are organized as a single genetic locus on 19pter
M Zimmer, RL Medcalf, TM Fink, C Mattmann, P Lichter, DE Jenne |
Proceedings of the National Academy of Sciences | 1992 |
Human neutrophil azurocidin synergizes with leukocyte elastase and cathepsin G in the killing of Capnocytophaga sputigena
KT Miyasaki, AL Bodeau |
Infection and immunity | 1992 |
Antineutrophil cytoplasmic antibodies: A still-growing class of autoantibodies in inflammatory disorders
CG Kallenberg, AH Mulder, JW Tervaert |
The American Journal of Medicine | 1992 |
Mononuclear Phagocytes
R van Furth |
1992 | |
Structure, chromosomal assignment, and expression of the gene for proteinase-3. The Wegener's granulomatosis autoantigen
AB Sturrock, KF Franklin, G Rao, BC Marshall, MB Rebentisch, RS Lemons, JR Hoidal |
The Journal of biological chemistry | 1992 |
Antineutrophil cytoplasmic antibodies (ANCA) directed against cathepsin G in ulcerative colitis, Crohn's disease and primary sclerosing cholangitis.
Halbwachs-Mecarelli L, Nusbaum P, Noël LH, Reumaux D, Erlinger S, Grünfeld JP, Lesavre P |
Clinical & Experimental Immunology | 1992 |
Interference of Wegener's granulomatosis autoantibodies with neutrophil Proteinase 3 activity.
van de Wiel BA, Dolman KM, van der Meer-Gerritsen CH, Hack CE, von dem Borne AE, Goldschmeding R |
Clinical & Experimental Immunology | 1992 |
Treatment of patients with chronic granulomatous disease with recombinant human interferon-gamma does not improve neutrophil oxidative metabolism, cytochrome b558 content or levels of four anti-microbial proteins.
Mühlebach TJ, Gabay J, Nathan CF, Erny C, Dopfer G, Schroten H, Wahn V, Seger RA |
Clinical & Experimental Immunology | 1992 |
In vitro killing of oral Capnocytophaga by granule fractions of human neutrophils is associated with cathepsin G activity
KT Miyasaki, AL Bodeau |
Journal of Clinical Investigation | 1991 |
Anti-Granulocyte Antibodies (C-ANCA, P-ANCA, GS-ANA) Studied by Confocal Scanning Laser Fluorescence Microscopy, ELISA, and Chemiluminescence Techniques
T Skogh, C Dahlgren, K Holmgren, E Peen, O Stendahl |
Scandinavian Journal of Immunology | 1991 |
Proteinases in Chronic Lung Infection
RA Stockley, SL Hill, D Burnett |
Annals of the New York Academy of Sciences | 1991 |
The Discovery and Biologic Properties of Cephalosporin-Based Inhibitors of PMN Elastase
P Davies, BM Ashe, RJ Bonney, C Dorn, P Finke, D Fletcher, WA Hanlon, JL Humes, A Maycock, RA Mumford, MA Navia, EE Opas, S Pacholok, S Shah, M Zimmerman, JB Doherty |
Annals of the New York Academy of Sciences | 1991 |
Covalent structure of two novel neutrophile leucocyte-derived proteins of porcine and human origin. Neutrophile elastase homologues with strong monocyte and fibroblast chemotactic activities
H FLODGAARD, E OSTERGAARD, S BAYNE, A SVENDSEN, J THOMSEN, M ENGELS, A WOLLMER |
European Journal of Biochemistry | 1991 |
Comparison of granule proteins from human polymorphonuclear leukocytes which are bactericidal toward Pseudomonas aeruginosa
KR Wasiluk, KM Skubitz, BH Gray |
Infection and immunity | 1991 |
Differential killing of Actinobacillus actinomycetemcomitans and Capnocytophaga spp. by human neutrophil granule components
KT Miyasaki, AL Bodeau, TF Flemmig |
Infection and immunity | 1991 |
Complementary DNA sequence of human neutrophil azurocidin, an antibiotic with extensive homology to serine proteases
RP Almeida, M Melchior, D Campanelli, C Nathan, JE Gabay |
Biochemical and Biophysical Research Communications | 1991 |
International Yearbook of Nephrology 1992
VE Andreucci, LG Fine |
1991 | |
Characterization of proteinase-3 (PR-3), a neutrophil serine proteinase. Structural and functional properties
NV Rao, NG Wehner, BC Marshall, WR Gray, BH Gray, JR Hoidal |
The Journal of biological chemistry | 1991 |
Antibiotic proteins of human neutrophils
JK Spitznagel |
Journal of Clinical Investigation | 1990 |
Monoclonal Antibodies Specific for Neutrophil Proteinase 4. Production and Use for Isolation of the Enyzme
K OHLSSON, C LINDER, M ROSENGREN |
Biological Chemistry Hoppe-Seyler | 1990 |
Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils
D Campanelli, M Melchior, Y Fu, M Nakata, H Shuman, C Nathan, JE Gabay |
Journal of Experimental Medicine | 1990 |
In vitro sensitivity of oral, gram-negative, facultative bacteria to the bactericidal activity of human neutrophil defensins
KT Miyasaki, AL Bodeau, T Ganz, ME Selsted, RI Lehrer |
Infection and immunity | 1990 |
Purification of macrophage deactivating factor
S Srimal, C Nathan |
Journal of Experimental Medicine | 1990 |
Amino acid sequence of CAP37, a human neutrophil granule-derived antibacterial and monocyte-specific chemotactic glycoprotein structurally similar to neutrophil elastase
J Pohl, HA Pereira, NM Martin, JK Spitznagel |
FEBS Letters | 1990 |
Isolation of two isoforms of a novel 15-kDa protein from rabbit polymorphonuclear leukocytes that modulate the antibacterial actions of other leukocyte proteins
CE Ooi, J Weiss, O Levy, P Elsbach |
The Journal of biological chemistry | 1990 |