Neutrophil elastase, proteinase 3 and cathepsin G: Physicochemical properties, activity and physiopathological functions

Korkmaz, Brice; Moreau, Thierry; Gauthier, Francis

doi:10.1016/j.biochi.2007.10.009

Cited by 415 publications

(405 citation statements)

References 199 publications

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“…Moreover, while increased ADAM8 expression has been reported in ADAM10-deficient mouse skin (37), comparable serum sIL-6R levels in ADAM8 knock-out mice also excluded ADAM8 as compensatory IL-6R sheddase. DPPI activates neutrophil elastase, cathepsin G as well as proteinase 3 by excising dipeptides from the N terminus (38). Notably, cathepsin G has previously been implicated in human IL-6R shedding in an inflammatory setting (39).…”

Section: Discussionmentioning

confidence: 99%

“…4C). The serine proteases neutrophil elastase, cathepsin G, and proteinase 3 are highly abundant in neutrophils and a subpopulation of monocytes (38). Furthermore, it has been reported that in human inflammatory lesions IL-6R is FIGURE 2.…”

Section: Adam17 Is the Major Sheddase Of Pma-and Lps-induced Il-6r Shmentioning

confidence: 99%

“…All three proteases must be activated by N-terminal removal of two amino acids, which is accomplished by dipeptidylpeptidase I (DPPI, or alternatively cathepsin C) (38). To analyze whether neutrophil elastase, cathepsin G, or proteinase 3 are involved in the generation of circulating sIL-6R generation we analyzed sIL-6R levels in the serum of DPPI knock-out mice, which lack neutrophil elastase, cathepsin G, and proteinase 3 activity (23).…”

Section: Adam17 Is the Major Sheddase Of Pma-and Lps-induced Il-6r Shmentioning

confidence: 99%

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Shedding of Endogenous Interleukin-6 Receptor (IL-6R) Is Governed by A Disintegrin and Metalloproteinase (ADAM) Proteases while a Full-length IL-6R Isoform Localizes to Circulating Microvesicles

Schumacher

Meyer

Mauermann

et al. 2015

Journal of Biological Chemistry

121

117

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Background:A soluble form of IL-6 receptor mediates pathogenic IL-6 trans-signaling. Results: ADAM10 and ADAM17 release IL-6 receptor from both human and murine monocytes/macrophages, whereas in the blood IL-6 receptor is also present on microvesicles. Conclusion: Shedding of endogenous IL-6 receptor is similar in humans and mice. Significance: Microvesicle release represents a novel mode of soluble IL-6 receptor generation with potential clinical implications.

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Section: Discussionmentioning

confidence: 99%

Section: Adam17 Is the Major Sheddase Of Pma-and Lps-induced Il-6r Shmentioning

confidence: 99%

Section: Adam17 Is the Major Sheddase Of Pma-and Lps-induced Il-6r Shmentioning

confidence: 99%

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Shedding of Endogenous Interleukin-6 Receptor (IL-6R) Is Governed by A Disintegrin and Metalloproteinase (ADAM) Proteases while a Full-length IL-6R Isoform Localizes to Circulating Microvesicles

Schumacher

Meyer

Mauermann

et al. 2015

Journal of Biological Chemistry

121

117

View full text Add to dashboard Cite

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“…The only exception is the very conservative Ile-208 substitution on the back side of the hPR3 molecule by a Val, which is one methyl group shorter. Active site residues K99, D61, and R143 implicated in the substrate binding of hPR3 and conferring its specificity are not substituted on gPR3 (24)(25)(26). Fig.…”

Section: Structural Characteristics Of Gpr3mentioning

confidence: 96%

Mapping of Conformational Epitopes on Human Proteinase 3, the Autoantigen of Wegener’s Granulomatosis

Kuhl

Korkmaz

Utecht³

et al. 2010

The Journal of Immunology

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Anti-neutrophil cytoplasmic Abs (cANCAs) against conformational epitopes of proteinase 3 (PR3) are regarded as an important pathogenic marker in Wegener’s granulomatosis (WG). Although the three-dimensional structure of PR3 is known, binding sites of mAbs and cANCAs have not been mapped to date. Competitive binding and biosensor experiments suggested the existence of four nonoverlapping areas on the PR3 surface. In this paper, we present an approach to identify these discontinuous surface regions that cannot be mimicked by linear peptides. The very few surface substitutions found in closely related PR3 homologs from primates, which were further varied by the construction of functional human-gibbon hybrids, resulted in the differential loss of three Ab binding sites, two of which were mapped to the N-terminal β-barrel and one to the linker segment connecting the N- and C-terminal barrels of PR3. The sera from WG patients differed in their binding to gibbon PR3 and the gibbon-human PR3 hybrid, and could be divided into two groups with similar or significantly reduced binding to gibbon PR3. Binding of almost all sera to PR3–α1-protease inhibitor (α1–PI) complexes was even more reduced and often absent, indicating that major antigenic determinants overlap with the active site surface on PR3 that associates with α1-PI. Similarly, the mouse mAbs CLB12.8 and 6A6 also did not react with gibbon PR3 and PR3–α1-PI complexes. Our data strongly suggest that cANCAs from WG patients at least in part recognize similar surface structures as do mouse mAbs and compete with the binding of α1-PI to PR3.

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“…Serine proteases derived from these cells, such as CMA1s, CG, and neutrophil elastase, have long been implicated in extracellular functions, such as inflammation and tissue remodeling. 87,88 Consequently, in addition to well-established roles in cytotoxicity, it is possible that lymphocyte-derived serine proteases modulate some of these extracellular processes as well.…”

Section: Additional Roles Of Grsmentioning

confidence: 99%

A quarter century of granzymes

2011

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Neutrophil elastase, proteinase 3 and cathepsin G: Physicochemical properties, activity and physiopathological functions

Cited by 415 publications

References 199 publications

Shedding of Endogenous Interleukin-6 Receptor (IL-6R) Is Governed by A Disintegrin and Metalloproteinase (ADAM) Proteases while a Full-length IL-6R Isoform Localizes to Circulating Microvesicles

Shedding of Endogenous Interleukin-6 Receptor (IL-6R) Is Governed by A Disintegrin and Metalloproteinase (ADAM) Proteases while a Full-length IL-6R Isoform Localizes to Circulating Microvesicles

Mapping of Conformational Epitopes on Human Proteinase 3, the Autoantigen of Wegener’s Granulomatosis

A quarter century of granzymes

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