Activation of progelatinase A (MMP-2) by neutrophil elastase, cathepsin G, and proteinase-3: A role for inflammatory cells in tumor invasion and angiogenesis

2001 ◽  
Vol 189 (2) ◽  
pp. 197-206 ◽  
Author(s):  
Peter Shamamian ◽  
Jess D. Schwartz ◽  
Ben J.Z. Pocock ◽  
Sara Monea ◽  
David Whiting ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Tumor Invasion ◽  
Inflammatory Cells ◽  
Cathepsin G ◽  
Proteinase 3

Unopposed Cathepsin G, Neutrophil Elastase, and Proteinase 3 Cause Severe Lung Damage and Emphysema

2014 ◽  
Vol 184 (8) ◽  
pp. 2197-2210 ◽  
Author(s):  
Nicolas Guyot ◽  
Julien Wartelle ◽  
Laurette Malleret ◽  
Alexandre A. Todorov ◽  
Gilles Devouassoux ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Cathepsin G ◽  
Lung Damage ◽  
Proteinase 3 ◽  
Severe Lung

Measurement of Neutrophil Elastase, Proteinase 3, and Cathepsin G Activities using Intramolecularly Quenched Fluorogenic Substrates

2011 ◽  
pp. 125-138 ◽  
Author(s):  
Brice Korkmaz ◽  
Sylvie Attucci ◽  
Christophe Epinette ◽  
Elodie Pitois ◽  
Marie-Lise Jourdan ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Cathepsin G ◽  
Proteinase 3 ◽  
Fluorogenic Substrates

Neutrophil elastase enzymatically antagonizes the in vitro action of G-CSF: implications for the regulation of granulopoiesis

Blood ◽  
2003 ◽  
Vol 101 (5) ◽  
pp. 1752-1758 ◽  
Author(s):  
Frank El Ouriaghli ◽  
Hiroshi Fujiwara ◽  
J. Joseph Melenhorst ◽  
Giuseppe Sconocchia ◽  
Nancy Hensel ◽  
...  
Keyword(s):  
Negative Feedback ◽  
Neutrophil Elastase ◽  
Serine Proteases ◽  
Cathepsin G ◽  
Proteinase 3 ◽  
Gm Csf ◽  
Cd34 Cells ◽  
Macrophage Colony ◽  
Serum Free Suspension

There is evidence that neutrophil production is a balance between the proliferative action of granulocyte–colony-stimulating factor (G-CSF) and a negative feedback from mature neutrophils (the chalone). Two neutrophil serine proteases have been implicated in granulopoietic regulation: pro–proteinase 3 inhibits granulocyte macrophage–colony-forming unit (CFU-GM) growth, and elastase mutations cause cyclic and congenital neutropenia. We further studied the action of the neutrophil serine proteases (proteinase 3, elastase, azurocidin, and cathepsin G) on granulopoiesis in vitro. Elastase inhibited CFU-GM in methylcellulose culture. In serum-free suspension cultures of CD34+ cells, elastase completely abrogated the proliferation induced by G-CSF but not that of GM-CSF or stem cell factor (SCF). The blocking effect of elastase was prevented by inhibition of its enzymatic activity with phenylmethylsulfonyl fluoride (PMSF) or heat treatment. When exposed to enzymatically active elastase, G-CSF, but not GM-CSF or SCF, was rapidly cleaved and rendered inactive. These results support a role for neutrophil elastase in providing negative feedback to granulopoiesis by direct antagonism of G-CSF.

scholarly journals Effect of DNase on the activity of neutrophil elastase, cathepsin G and proteinase 3 in the presence of DNA

FEBS Letters ◽  
2000 ◽  
Vol 473 (2) ◽  
pp. 154-156 ◽  
Author(s):  
Jérôme Duranton ◽  
Didier Belorgey ◽  
Jacqueline Carrère ◽  
Lionel Donato ◽  
Thomas Moritz ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Cathepsin G ◽  
Proteinase 3

scholarly journals Local structural plasticity of the Staphylococcus aureus evasion protein EapH1 enables engagement with multiple neutrophil serine proteases

2020 ◽  
Vol 295 (22) ◽  
pp. 7753-7762 ◽  
Author(s):  
Timothy J. Herdendorf ◽  
Daphne A. C. Stapels ◽  
Suzan H. M. Rooijakkers ◽  
Brian V. Geisbrecht
Keyword(s):  
Staphylococcus Aureus ◽  
Active Site ◽  
Neutrophil Elastase ◽  
Serine Proteases ◽  
Noncovalent Complex ◽  
Structural Plasticity ◽  
Binding Mode ◽  
Cathepsin G ◽  
Proteinase 3 ◽  
High Affinity

Members of the EAP family of Staphylococcus aureus immune evasion proteins potently inhibit the neutrophil serine proteases (NSPs) neutrophil elastase, cathepsin-G, and proteinase-3. Previously, we determined a 1.8 Å resolution crystal structure of the EAP family member EapH1 bound to neutrophil elastase. This structure revealed that EapH1 blocks access to the enzyme's active site by forming a noncovalent complex with this host protease. To determine how EapH1 inhibits other NSPs, we studied here the effects of EapH1 on cathepsin-G. We found that EapH1 inhibits cathepsin-G with a Ki of 9.8 ± 4.7 nm. Although this Ki value is ∼466-fold weaker than the Ki for EapH1 inhibition of neutrophil elastase, the time dependence of inhibition was maintained. To define the physical basis for EapH1's inhibition of cathepsin-G, we crystallized EapH1 bound to this protease, solved the structure at 1.6 Å resolution, and refined the model to Rwork and Rfree values of 17.4% and 20.9%, respectively. This structure revealed a protease-binding mode for EapH1 with cathepsin-G that was globally similar to that seen in the previously determined EapH1–neutrophil elastase structure. The nature of the intermolecular interactions formed by EapH1 with cathepsin-G differed considerably from that with neutrophil elastase, however, with far greater contributions from the inhibitor backbone in the cathepsin-G–bound form. Together, these results reveal that EapH1's ability to form high-affinity interactions with multiple NSP targets is due to its remarkable level of local structural plasticity.

Using a Caesalpinia echinata Lam. protease inhibitor as a tool for studying the roles of neutrophil elastase, cathepsin G and proteinase 3 in pulmonary edema

2013 ◽  
Vol 96 ◽  
pp. 235-243 ◽  
Author(s):  
Ilana Cruz-Silva ◽  
Christiane Neuhof ◽  
Andrezza Justino Gozzo ◽  
Viviane Abreu Nunes ◽  
Izaura Yoshico Hirata ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Pulmonary Edema ◽  
Neutrophil Elastase ◽  
Cathepsin G ◽  
Proteinase 3 ◽  
Caesalpinia Echinata

scholarly journals Neutrophil Elastase, Proteinase 3, and Cathepsin G as Therapeutic Targets in Human Diseases

2010 ◽  
Vol 62 (4) ◽  
pp. 726-759 ◽  
Author(s):  
Brice Korkmaz ◽  
Marshall S. Horwitz ◽  
Dieter E. Jenne ◽  
Francis Gauthier
Keyword(s):  
Neutrophil Elastase ◽  
Therapeutic Targets ◽  
Cathepsin G ◽  
Human Diseases ◽  
Proteinase 3

Defective Expression of Neutrophil Serine Proteases in Myeloid Progenitors of Congenital Neutropenia Patients Carrying Either ELA2 or HAX1 Mutations.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3299-3299 ◽  
Author(s):  
Julia Skokowa ◽  
John-Paul Fobiwe ◽  
Dan Lan ◽  
Manuela Germeshausen ◽  
Karl Welte
Keyword(s):  
Mrna Expression ◽  
Neutrophil Elastase ◽  
Cathepsin D ◽  
Serine Proteases ◽  
Cathepsin G ◽  
Proteinase 3 ◽  
Congenital Neutropenia ◽  
Expression Levels ◽  
Patient Groups ◽  
Mrna Expression Levels

Abstract Severe congenital neutropenia (CN) is a heterogeneous disorder of myelopoiesis with two major types of inheritance: autosomal dominant CN defined by mutations in ELA2 gene encoding neutrophil elastase (NE) (Horwitz M., et al., Nat Genet.1999;23:433) and autosomal recessive CN (including Kostmann syndrome) carrying HAX-1 mutations (Klein C., et al., Nat Genet.2007;39:86), both characterized by a maturation arrest of granulopoiesis at the level of promyelocytes. In the present study we aimed to evaluate the expression profile of genes specifically expressed in the CD33+ bone marrow promyelocytes of both patient groups harbouring ELA2 or HAX1 mutations. In healthy individuals mRNA expression levels of neutrophil serine proteases (neutrophil elastase (ELA2), cathepsin G, cathepsin D, proteinase 3 and azurocidin) as well as of myeloperoxidase (MPO) and defensins reached highest levels in the azurophil granules at the promyelocytic stage of neutrophil differentiation (Borregaard N., et al., Curr Opin Hematol.2001;8:23). We found downregulation of mRNA expression levels of ELA2 (8.9 fold), cathepsin G (7.6 fold), cathepsin D (11.2 fold), proteinase 3 (9.2 fold) and defensin B1 (6.5 fold) in both groups of CN patients (with ELA2 or HAX1 mutations), in comparison to G-CSF-treated patients with idiopathic neutropenia (IN) and G-CSF-treated healthy controls. In contrast, there were no difference in mRNA expression levels of azurocidin and only slight decrease in the expression of MPO mRNA in CN patients. Additionally, we found significantly reduced protein levels of neutrophil elastase (NE) in plasma of CN patients irrespective of “ELA2 or HAX1” inheritance, in comparison to cyclic neutropenia (CyN) patients, IN patients and G-CSF-treated healthy controls. Taken together, both ELA2 and HAX1 mutations are associated with defective expression of neutrophil serine proteases such as NE, cathepsin G, cathepsin D, proteinase 3 as well as of defensin B1 in CD33+ myeloid progenitor cells of CN patients, suggesting a common pathway for both patient groups. Intriguingly, ELA2 expression is directly regulated by LEF-1, suggesting that abrogated LEF-1 expression in CN promyelocytes (Skokowa J., et al., Nat. Med.2006;12:1191) may be responsible for defective serine proteases expression in both groups, since all are regulated by a similar mechanism.

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