Degradation products of fibrinogen by elastase-like neutral protease from human granulocytes. Characterization and effects on blood coagulation in vitro.

Gramse, M.; Bingenheimer, C; Schmidt, W; Egbring, R; Havemann, K

doi:10.1172/jci109001

Cited by 67 publications

(23 citation statements)

References 19 publications

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“…These data confirm previous reports that crude leukocyte extracts contain neutral proteinases capable of degrading fibrinogen (6,14,(16)(17)(18)(19)(20)(21) and releasing an FPA-containing fragment from the NH2-terminal region of the fibrinogen Ac-chain (14). We have extended these observations by demonstrating that HNE is the enzyme responsible for the fibrinogenolytic activity ofthe extracts and for the release of the FPA-containing fragment.…”

Section: Discussionsupporting

confidence: 91%

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Development of an assay for in vivo human neutrophil elastase activity. Increased elastase activity in patients with alpha 1-proteinase inhibitor deficiency.

Weitz¹,

Landman²,

Crowley³

et al. 1986

J. Clin. Invest.

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Leukocyte extracts contain enzymes that digest fibrinogen and release a fibrinopeptide A-containing fragment. This study was undertaken to identify the responsible proteinase and to characterize the fibrinopeptide A-containing fragment so that it could be used as an index of enzyme activity. Both the fibrinogenolytic activity and the release of the fibrinopeptide A-containing fragment mediated by the leukocyte extracts were shown to be due to human neutrophil elastase (HNE) by the following criteria: activity was completely blocked by a specific HNE inhibitor or by adsorbing HNE from the extracts with a monospecific antibody and reconstitution with purified HNE restored the ability to release the fibrinopeptide A-containing fragment. This fragment was not released by a variety of other proteinases or by HNE-inhibitor complexes indicating that, at least with respect to the enzymes tested, it is a specific product of HNE and its release requires the free enzyme. By separating the products of HNE digestion of fibrinogen using high performance liquid chromatography, identifying the immunoreactive fractions and subjecting them to amino acid analysis, the fragment was identified as Aal-21, indicating an HNE cleavage site at the Val(Aa21)-Glu(Aa22) bond. The mean plasma Aal-21 level was markedly higher in patients with a1-proteinase inhibitor deficiency as compared to healthy controls (0.2 nM vs. 7.9 nM; P < 0.0001), consistent with increased in vivo HNE activity in these individuals.

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Section: Discussionsupporting

confidence: 91%

“…In contrast, leukocyte extracts release FPA and FPB-containing fragments (14). Additionally, the fibrinogen degradation products produced by leukocyte proteinases are structurally (6,14,16), immunochemically (17), and functionally (16) distinct from plasmin-derived cleavage products.…”

Section: Introductionmentioning

confidence: 99%

Development of an assay for in vivo human neutrophil elastase activity. Increased elastase activity in patients with alpha 1-proteinase inhibitor deficiency.

Weitz¹,

Landman²,

Crowley³

et al. 1986

J. Clin. Invest.

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“…A variety of neutral proteases (5,(14)(15)(16)(17)(18) and acidic cathepsins (3) of neutrophils are capable of degrading fibrin (ogen). Within leukocyte granules, elastase has been identified as one of the major fibrinolytic proteases active at neutral pH (19).…”

mentioning

confidence: 99%

Leukocyte Elastase Release during Blood Coagulation

Plow¹

1982

J. Clin. Invest.

184

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A B S T R A C T Immunological detection of elastase, an enzyme present within leukocyte granules, has been used as a marker for polymorphonuclear leukocyte activation. Polymorphonuclear leukocytes contained 4.6 gg/107 cells, whereas erythrocytes, mononuclear cells, and platelets contained < 1% of this level. In plasma that was separated from blood cells after 1 h at 22°C, the mean level of elastase-related antigen in seven normal donors was 25±6 ng/ml. This level was unaltered by immediate separation of the plasma from the cells, by inclusion of protease inhibitors, or by anticoagulation of the plasma with either EDTA or acidcitrate-dextrose (the level in heparinized plasma was approximately threefold higher). In serum, the level of elastase-related antigen was 288±125 ng/ml, representing an 11.5-fold increase above plasma levels. The antigen detected in serum was immunochemically indistinguishable from the leukocyte enzyme. Release of elastase was observed when isolated polymorphonuclear leukocytes were added to nonanticoagulated platelet-rich or platelet-poor plasma, recalcified plasma, or to serum. Addition of a chelating agent to serum prevented elastase release, but calcium or magnesium did not induce release in the absence of plasma. Coagulation induced by addition of thrombin to plasma also failed to induce release. In whole blood or in anticoagulated plasma reconstituted with polymorphonuclear leukocytes and then recalcified, initial release of elastase occurred concomitantly with or slightly after clotting and reached maximal levels within 20-40 min after clot formation. The data indicates that early events in coagulation or other pathways that occur in parallel with coagulation induce leukocyte release. The release of elastase, a major fibrinolytic protease of leukocytes, from the cells provides a mechanism Portions of this study were presented at the

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“…A granulocyte discharges the protease when irritated by phagocytes or when suffering any damage. The elastase decomposes the connective tissue protein, immunoglobulins, and other proteins which are components of the coagulation system, and therefore causes exacerbation of tissue injury [4]. It is possible to obtain information such as the extent of inflammation and effects of therapy by quantitative measurement of this enzyme [5].…”

Section: Yagi Et Almentioning

confidence: 99%

Serum Granulocytic Elastase and Superoxide Dismutase Activity after Administration of Protease-Inhibitor to Postoperative Patients

Yagi

Tomita

Onoda

et al. 1989

J. Clin. Biochem. Nutr.

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SummaryPostroperative changes in the plasma levels of granulocytic elastase and superoxide dismutase were examined clinically. Seven patients who had undergone cholecystectomy and eight patients who had undergone subtotal esophageal resection were considered. The protease inhibitor ulinastatin was administered to four of the latter patients. The levels of granulocytic elastase were elevated, and those of superoxide dismutase, decreased, in the non-medicated patients who had undergone esophageal resection (p<0.05). Furthermore, in the patients given the daily medication of 3 X 105 units of urinastatin for more than 3 days postoperatively, the elevation of granulocytic elastase levels and the decline of the superoxide dismutase levels were markedly suppressed (p<0.05). On the other hand, granulocytic elastase levels of the plasma to which ulinastatin had been added in vitro did not decrease. It is considered that the medicament of ulinastatin may be useful in the prevention of tissue injury caused by granulocytic elastase in cases where a disproportion of proteases and endogenous protease inhibitors exists.

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Degradation products of fibrinogen by elastase-like neutral protease from human granulocytes. Characterization and effects on blood coagulation in vitro.

Cited by 67 publications

References 19 publications

Development of an assay for in vivo human neutrophil elastase activity. Increased elastase activity in patients with alpha 1-proteinase inhibitor deficiency.

Development of an assay for in vivo human neutrophil elastase activity. Increased elastase activity in patients with alpha 1-proteinase inhibitor deficiency.

Leukocyte Elastase Release during Blood Coagulation

Serum Granulocytic Elastase and Superoxide Dismutase Activity after Administration of Protease-Inhibitor to Postoperative Patients

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