Cocaine-induced midline destruction

ABSTRACT In patients presenting with nasal septum perforation, the differential diagnosis between ANCA-associated vasculitis and cocaine-induced midline destruction (CIMD) can be challenging. We describe the case of a 28-year old man who presented with a nasal septum perforation. He admitted the use of cocaine and showed no other symptoms of systemic inflammation. Perinuclear anti-neutrophilic cytoplasmatic antibodies (p-ANCAs) came back positive, as did anti-proteinase 3-antibodies. Further testing revealed antibodies to human neutrophil elastase (HNE), typically found in CIMD but rarely in ANCA-associated vasculitis. The combination of an atypical ANCA-pattern and the detection of HNE-antibodies led to the diagnosis of CIMD. In conclusion, HNE antibodies can be used to distinguish between CIMD and ANCA-associated vasculitis.

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Extended Cleavage Specificity of Human Neutrophil Elastase, Human Proteinase 3, and Their Distant Ortholog Clawed Frog PR3—Three Elastases With Similar Primary but Different Extended Specificities and Stability

Frontiers in Immunology ◽

10.3389/fimmu.2018.02387 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 14

Author(s):

Zhirong Fu ◽

Michael Thorpe ◽

Srinivas Akula ◽

Gurdeep Chahal ◽

Lars T. Hellman

Keyword(s):

Neutrophil Elastase ◽

Human Neutrophil ◽

Human Neutrophil Elastase ◽

Proteinase 3 ◽

Cleavage Specificity ◽

Clawed Frog

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N-ArylacylO-sulfonated aminoglycosides as novel inhibitors of human neutrophil elastase, cathepsin G and proteinase 3

Glycobiology ◽

10.1093/glycob/cww011 ◽

2016 ◽

Vol 26 (7) ◽

pp. 701-709 ◽

Cited By ~ 13

Author(s):

Ioana Craciun ◽

Amanda M Fenner ◽

Robert J Kerns

Keyword(s):

Neutrophil Elastase ◽

Human Neutrophil ◽

Cathepsin G ◽

Human Neutrophil Elastase ◽

Proteinase 3

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A new proteinase 3 substrate with improved selectivity over human neutrophil elastase

Analytical Biochemistry ◽

10.1016/j.ab.2013.07.028 ◽

2013 ◽

Vol 442 (1) ◽

pp. 75-82 ◽

Cited By ~ 13

Author(s):

J. Popow-Stellmaszyk ◽

M. Wysocka ◽

A. Lesner ◽

B. Korkmaz ◽

K. Rolka

Keyword(s):

Neutrophil Elastase ◽

Human Neutrophil ◽

Human Neutrophil Elastase ◽

Proteinase 3

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Structural and functional characterization of elastases from horse neutrophils

Biochemical Journal ◽

10.1042/bj3000401 ◽

1994 ◽

Vol 300 (2) ◽

pp. 401-406 ◽

Cited By ~ 9

Author(s):

A Dubin ◽

J Potempa ◽

J Travis

Keyword(s):

Neutrophil Elastase ◽

Human Neutrophil ◽

Proteinase Inhibitors ◽

Functional Characterization ◽

Human Neutrophils ◽

Human Neutrophil Elastase ◽

Proteinase 3 ◽

Reactive Site ◽

Chronic Lung Diseases

In order better to understand the pathophysiology of the equine form of emphysema, two elastinolytic enzymes from horse neutrophils, referred to as proteinases 2A and 2B, have been extensively characterized and compared with the human neutrophil proteinases, proteinase-3 and elastase. Specificity studies using both the oxidized insulin B-chain and synthetic peptides revealed that cleavage of peptide bonds with P1 alanine or valine residues was preferred. Further characterization of the two horse elastases by N-terminal sequence and reactive-site analyses indicated that proteinases 2A and 2B have considerable sequence similarity to each other, to proteinase-3 from human neutrophils (proteinase 2A), to human neutrophil elastase (proteinase 2B) and to a lesser extent to pig pancreatic elastase. Horse and human elastases differed somewhat in their interaction with some natural protein proteinase inhibitors. For example, in contrast with its action on human neutrophil elastase, aprotinin did not inhibit either of the horse proteinases. However, the Val15, alpha-aminobutyric acid-15 (Abu15), alpha-aminovaleric acid-15 (Nva15) and Ala15 reactive-site variants of aprotinin were good inhibitors of proteinase 2B (Ki < 10(-9) M) but only weak inhibitors of proteinase 2A (Ki > 10(-7) M). In summary, despite these differences, the horse neutrophil elastases were found to resemble closely their human counterparts, thus implicating them in the pathological degradation of connective tissue in chronic lung diseases in the equine species.

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Widening the Applicability of Human Neutrophil Elastase and Proteinase 3 Peptide Vaccines by Elucidating Immunogenic Non-HLA-A2 MHC Class I Restricted Epitopes.

Blood ◽

10.1182/blood.v108.11.3708.3708 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3708-3708

Author(s):

Rachel E. Hewitt ◽

J. Joseph Melenhorst ◽

David A. Price ◽

Emma Gostick ◽

Nancy F. Hensel ◽

...

Keyword(s):

Amino Acids ◽

T Cell ◽

Cell Lines ◽

Neutrophil Elastase ◽

Human Neutrophil ◽

Peptide Sequence ◽

Human Neutrophil Elastase ◽

Proteinase 3 ◽

Short Term ◽

T Cell Lines

Abstract Human Neutrophil Elastase (HNE) and proteinase 3 (Pr3) belong to a group of myeloid tissue restricted serine proteases, aberrantly expressed by myeloid leukemia cells of interest as a source of myeloid-restricted antigens applicable to immunization strategies. HNE shares with Pr3 the antigenic PR1 peptide sequence inducing HLA-A*0201 restricted cytotoxic T cells (CTL) against leukemic cells. Our previous studies with full length HNE protein have demonstrated its potential for inducing both CD4+ and CD8+ T cell responses in healthy individuals including HLA-A2 negative individuals, suggesting an immunogenic potential of HNE beyond the PR1 peptide (Fujiwara H et al Blood 2004). To find epitopes other than PR1 in HNE and Pr3, peripheral blood mononuclear cells (PBMC) from 15 AML patients were screened at diagnosis or relapse with a peptide matrix consisting of 15mers overlapping by 11 amino acids spanning HNE and Pr3.The corresponding Pr3 and HNE 15mers were also used to generate and test short term T cell lines derived from patient samples. Responses to the peptide matrix pools were measured by a CFSE flow cytometry-based proliferation assay where the proliferating fraction in response to peptide pools was compared to the background co-stimulatory antibody only control for each assay. A positive response was defined as a proliferating fraction minimum 0.1% of the total CD8/CD3 population after subtraction of background proliferation and at least one and a half times background for each assay. These steps helped to control for variability between samples. Using this strategy we identified PR1 and 6 new candidate epitopes contained within HNE and Pr3. Corresponding immunogenic Pr3 sequences in 2 epitopes differed by only 3 amino acids from the immunogenic HNE sequence. CD8 short term T cell lines generated to these epitopes were restricted by HLA-A2, B35 and A68. Optimal peptide length was predicted using RANKPEP (http://www.mifoundation.org/Tools/rankpep.html) and confirmed with flow cytometric assays measuring responses to candidate epitopes, by interferon-gamma, tumor necrosis factor-alpha, IL-2 production and degranulation in response to HLA-matched or mismatched EBV-transformed B cell antigen-presenting cells pulsed with relevant and irrelevant peptides. This study confirms the presence of multiple immunogenic epitopes in HNE and Pr3 and represents the first step in developing a multi-peptide leukemia vaccine broadly applicable to individuals of diverse HLA type.

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Discriminating between the Activities of Human Neutrophil Elastase and Proteinase 3 Using Serpin-derived Fluorogenic Substrates

Journal of Biological Chemistry ◽

10.1074/jbc.m202918200 ◽

2002 ◽

Vol 277 (42) ◽

pp. 39074-39081 ◽

Cited By ~ 34

Author(s):

Brice Korkmaz ◽

Sylvie Attucci ◽

Eric Hazouard ◽

Martine Ferrandière ◽

Marie Lise Jourdan ◽

...

Keyword(s):

Neutrophil Elastase ◽

Human Neutrophil ◽

Human Neutrophil Elastase ◽

Proteinase 3 ◽

Fluorogenic Substrates

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Potent and Broad but not Unselective Cleavage of Cytokines and Chemokines by Human Neutrophil Elastase and Proteinase 3

International Journal of Molecular Sciences ◽

10.3390/ijms21020651 ◽

2020 ◽

Vol 21 (2) ◽

pp. 651 ◽

Cited By ~ 1

Author(s):

Zhirong Fu ◽

Srinivas Akula ◽

Michael Thorpe ◽

Lars Hellman

Keyword(s):

Mast Cell ◽

Neutrophil Elastase ◽

Human Neutrophil ◽

Serine Proteases ◽

General Pattern ◽

Neutrophil Activation ◽

Cathepsin G ◽

Human Neutrophil Elastase ◽

Proteinase 3 ◽

Cytokines And Chemokines

In two recent studies we have shown that three of the most abundant human hematopoietic serine proteases—mast cell chymase, mast cell tryptase and neutrophil cathepsin G—show a highly selective cleavage of cytokines and chemokines with a strong preference for a few alarmins, including IL-18, TSLP and IL-33. To determine if this is a general pattern for many of the hematopoietic serine proteases we have analyzed the human neutrophil elastase (hNE) and human proteinase 3 (hPR-3) for their cleavage of a panel of 69 different human cytokines and chemokines. Our results showed that these two latter enzymes, in sharp contrast to the two previous, had a very potent and relatively unrestrictive cleavage on this panel of targets. Almost all of these proteins were cleaved and many of them were fully degraded. In light of the proteases abundance and their colocalization, it is likely that together they have a very potent degrading activity on almost any protein in the area of neutrophil activation and granule release, including both foreign bacterial or viral proteins as well as various self-proteins in the area of inflammation/infection. However, a few very interesting exceptions to this pattern were found indicating a high resistance to degradation of some cytokines and chemokines, including TNF-α, IL-5, M-CSF, Rantes, IL-8 and MCP-1. All of these are either important for monocyte-macrophage, neutrophil or eosinophil proliferation, recruitment and activation, suggesting that cytokines/chemokines and proteases may have coevolved to not block the recruitment of monocytes–macrophages, neutrophils and possibly eosinophils during an inflammatory response involving neutrophil activation.

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