Degradation of fibronectin by human leukocyte elastase. Release of biologically active fragments.

McDonald, John A.; Kelley, D G

doi:10.1016/s0021-9258(18)43580-6

Cited by 351 publications

(52 citation statements)

References 49 publications

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“…Events directly related to unopposed elastase activity include cleavage of coagulation factors, complement, immunoglobulins, and cell surface receptors such as CXCR1 [79][80][81][82] (Figure 3). Antimicrobial peptides , elastin 84 , collagen 85 , fibronectin 86 and proteoglycan 87 have also been reported to be cleaved by elastase. Some of the gene expression changes that occur in cells responding to elastase include increased matrix metalloprotease and cathepsin expression mediated via elastase-induced activation of TACE-and Meprin-mediated EGFR signalling [88][89][90][91] .…”

Section: [H1] Mechanisms/pathophysiologymentioning

confidence: 99%

α1-Antitrypsin deficiency

Greene

Marciniak

Teckman

et al. 2016

Nat Rev Dis Primers

244

204

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α1-Antitrypsin deficiency (A1ATD) is an inherited disorder caused by mutations in SERPINA1, leading to liver and lung disease. It is not a rare disorder but frequently goes underdiagnosed or misdiagnosed as asthma, chronic obstructive pulmonary disease (COPD) or cryptogenic liver disease. The most frequent disease-associated mutations include the S allele and the Z allele of SERPINA1, which lead to the accumulation of misfolded α1-antitrypsin in hepatocytes, endoplasmic reticulum stress, low circulating levels of α1-antitrypsin and liver disease. Currently, there is no cure for severe liver disease and the only management option is liver transplantation when liver failure is life-threatening. A1ATD-associated lung disease predominately occurs in adults and is caused principally by inadequate protease inhibition. Treatment of A1ATD-associated lung disease includes standard therapies that are also used for the treatment of COPD, in addition to the use of augmentation therapy (that is, infusions of human plasma-derived, purified α1-antitrypsin). New therapies that target the misfolded α1-antitrypsin or attempt to correct the underlying genetic mutation are currently under development.

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Section: [H1] Mechanisms/pathophysiologymentioning

confidence: 99%

α1-Antitrypsin deficiency

Greene

Marciniak

Teckman

et al. 2016

Nat Rev Dis Primers

244

204

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“…The SDS-PAGE pattern for the immunoglobulins, fibronectin, a1-protease inhibitor, a2macroglobulin, and unfolded type I collagen showed large fragments even after prolonged digestion. For fibronectin, what we see on the gel may correspond to at least three domains (18) or may resemble the three polypeptides released by limited proteolysis with human leukocyte elastase (15). We have previously shown the substrate specificity for FIG.…”

Section: Discussionmentioning

confidence: 83%

Degradation of protease inhibitors, immunoglobulins, and other serum proteins by Serratia protease and its toxicity to fibroblast in culture

Molla¹,

Matsumoto²,

Oyamada³

et al. 1986

Infect Immun

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We investigated the effect of the extracellular protease of Serratia marcescens on human serum constituents such as immunoglobulins, fibronectin, alpha 1-protease inhibitor, alpha 2-macroglobulin, lysozyme, and transferrin. At a very low concentration of Serratia 56-kilodalton protease (56K protease), purified human plasma fibronectin was degraded rapidly into three structural domains or small fragments. Immunoglobulin G3 (IgG3) and IgA1 were also degraded within 30 min with 1 microgram of this protease per ml, more rapidly than their other subclass of IgG or IgA. alpha 1-Protease inhibitor, which did not inhibit the 56K protease, was degraded similarly by the protease. These events were demonstrated by fluorescence polarization and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protease was considerably inhibited by human alpha 2-macroglobulin and chicken ovomacroglobulin. However, when there was a 2 M excess of ovomacroglobulin or a 4 M excess of alpha 2-macroglobulin over the 56K protease, about 25 or 40% proteolytic activity remained, respectively. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the protease degraded the alpha 2-macroglobulin extensively during prolonged incubation, which paralleled with regeneration of the protease activity. The protease also cleaved human lysozyme, although moderately. Human serum transferrin was degraded slightly, and human serum albumin was almost resistant to the 56K protease. The enzyme seemed to have no effect on reconstituted collagen, but it degraded rat tropocollagen and yielded fragments of beta and gamma chains by cleaving the intramolecular cross-links. Most of the above proteolysis by the 56K protease appears to result in a limited type of substrate specificity. Thus, the present study demonstrates that the protease is capable of degrading defense-oriented humoral proteins and tissue constituents. Furthermore, it is toxic to fibroblasts. These findings also clarified the possible role of Serratia protease as a virulence factor in the pathogenesis of serratial infections. We recently demonstrated this notion in vivo with rabbit cornea (R. Kamata et al., Ophthalmology 92:1452-1459, 1985).

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“…NE is a serine protease which degrades a broad spectrum of extracellular matrix (ECM) and cell surface proteins, such as elastin, interstitial collagens, proteoglycans, fibronectin, laminin, and type IV collagens (2)(3)(4)(5). Under physiological damaged circumstances, such as presence of neoplasm, surgical stress and inflammation, the balance between elastase and antiprotease is collapsed, and the predominant elastolytic activity causes the destruction of ECM.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil elastase induces cell proliferation and migration by the release of TGF-α, PDGF and VEGF in esophageal cell lines

Wada

Yoshida²,

Tsutani³

et al. 2007

Oncol Rep

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Rapid regrowth or recurrent growth of occult cancer cells are often observed after esophagectomy or postoperative complications. In order to clarify the mechanism of such oncological circumstances, we focused on neutrophil elastase (NE), which degrades a broad spectrum of extracellular matrix and cell surface proteins. In the present study, we demonstrated that NE stimulated the growth of all of the five esophageal cell lines (TE-1, -7, -8, -12 and -13) by MTT assay and promoted cell invasion by cell migration assay. Protransforming growth factor-• (pro-TGF-•) from the cell membrane was released to the culture medium as a mature form after treatment with 5 μg/ml NE, and it reached the maximum level of 153% compared to the control values at 15 min of treatment in TE-13 cells. The phosphorylation of epidermal growth factor receptor (EGFR) rapidly occurs after treatment with NE and triggered the extracellular signalregulated kinases 1 and 2 (ERK) signaling pathway. Moreover, NE induced release of platelet-derived growth factor-AA (PDGF-AA), PDGF-BB and vascular endothelial growth factor (VEGF) to 141.9, 227.7, and 171.6% of the control values, respectively. A specific NE inhibitor, sivelestat, significantly inhibited the NE-induced cell proliferation, cell invasion and subsequently inhibited the signal transduction pathway. Furthermore, sivelestat significantly inhibited NE-induced release of TGF-•, PDGF-AA, PDGF-BB and VEGF in the medium in TE-13 esophageal carcinoma cells. These results strongly indicate that NE released from activated neutrophils stimulates the growth and progression of esophageal cancer cells by releasing the growth factors on the cell surface and that sivelestat, a specific NE inhibitor, blocks these processes. Furthermore, we postulate that postoperative administration of sivelestat might be useful as a new molecular-targeting cancer therapy as well as for the treatment of postoperative respiratory complications.

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Degradation of fibronectin by human leukocyte elastase. Release of biologically active fragments.

Cited by 351 publications

References 49 publications

α1-Antitrypsin deficiency

α1-Antitrypsin deficiency

Degradation of protease inhibitors, immunoglobulins, and other serum proteins by Serratia protease and its toxicity to fibroblast in culture

Neutrophil elastase induces cell proliferation and migration by the release of TGF-α, PDGF and VEGF in esophageal cell lines

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