Proteinases and their Inhibitors in Septicemia - Basic Concepts and Clinical Implications

Jochum, Marianne; Duswald, Karl-Heimo; Neumann, Siegfried; Witte, J.; Fritz, Hans

doi:10.1007/978-1-4615-9355-3_34

Cited by 53 publications

(21 citation statements)

References 7 publications

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“…This is an important finding that goes beyond physiological and pathological conditions. Moreover, with respect to the successive release of MMPs from residual leukocytes during storage (9,45,46,49), degradation of plasma proteins by MMP-8, MMP-9, MMP-12, and MMP-13 may occur when administering red cell concentrates to patients.…”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinases Collagenase-2, Macrophage Elastase, Collagenase-3, and Membrane Type 1-Matrix Metalloproteinase Impair Clotting by Degradation of Fibrinogen and Factor XII

Hiller

Lichte

Oberpichler

et al. 2000

Journal of Biological Chemistry

121

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The effects of plasma proteins on controlling the activity of matrix metalloproteinases (MMPs, matrixins) have been the focus of numerous studies, although only a few have examined the influence of matrixins on plasma proteins. Recently, it has been shown that MMPs may play a role in the degradation of fibrin. We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system. Our data demonstrate that the catalytic domains of MMP-8, MMP-12, MMP-13, and MMP-14 can proteolytically process fibrinogen and, with the exception of MMP-8, also inactivate Factor XII (Hageman factor). We have identified the amino termini of the major protein fragments. Cleavage of fibrinogen occurred in all chains and resulted in significantly impaired clotting. Moreover, rapid proteolytic inactivation of Factor XII (Hageman factor) by MMP-12, MMP-13, and MMP-14 was noted. These results support the hypothesis of an impaired thrombolytic potential of MMP-degraded Factor XII in vivo. MMPinduced degradation of fibrinogen supports a plasminindependent fibrinolysis mechanism. Consequently, degradation of these proteins may be important in inflammation, atherosclerosis, and angiogenesis, all of which are known to be influenced by MMP activity.The matrix metalloproteinases, MMPs 1 and matrixins, form a family of structurally and functionally related zinc-containing endopeptidases. Together they are able to degrade most of the constituents of the extracellular matrix such as basement membrane, collagens, proteoglycans, fibronectin, and laminin (1). Thus, they are implicated in connective tissue remodeling processes associated with embryonic development, pregnancy, growth, and wound repair (2). The deleterious potential of the MMPs is normally controlled by the endogenous and specific tissue inhibitors of metalloproteinases or the more general nonspecific ␣ 2 -macroglobulin (3). Disturbance of the well balanced equilibrium of MMPs and tissue inhibitors of metalloproteinases results in pathological situations such as rheumatoid and osteoarthritis, atherosclerosis, tumor growth, metastasis, and fibrosis (4-8). In addition to degradation of extracellular matrix constituents, plasma proteins such as serpins (9) or fibrinogen and cross-linked fibrin (10-12) are also cleaved.Fibrinogen is a 340-kDa dimeric glycoprotein consisting of a pair of three polypeptide chains A␣, B␤, and ␥ that are interconnected by 29 disulfide bonds. The amino termini of these chains are joined together in a central domain that can be isolated as a single fragment from a plasmin digestion of fibrinogen (13). During blood coagulation, fibrinogen participates in both the cellular phase and the fluid phase of blood clot formation (14, 15). Fibrinogen can be converted into an insoluble fibrin clot as a consequence of thrombin-catalyzed removal of fibrinopeptides A (FpA, A␣-(20 -35)) 2 and B (FpB...

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Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinases Collagenase-2, Macrophage Elastase, Collagenase-3, and Membrane Type 1-Matrix Metalloproteinase Impair Clotting by Degradation of Fibrinogen and Factor XII

Hiller

Lichte

Oberpichler

et al. 2000

Journal of Biological Chemistry

121

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“…Fast-reacting proteins (C-reactive protein, ai-antichymotrypsin, ct|-acid glycoprotein) were compara ble with the other slow-reacting proteins (haptoglobin, ai-antitrypsin). It has been shown that monitoring of E-cq PI levels, postoperatively, may be important for patients with septicemia [12], Furthermore, a de crease of C I2M and an increase of E-ci|PI, cqantitrypsin or C-reactive protein are of prog nostic value for patients with major compli cations [5,6,8,12,15], In the present study, no serious complications were observed, and there was no clinical difference between aprotinin-pretreated and -untreated patients. Nevertheless, the results of the comparison of different plasma proteinases, proteinase inhibitors and other selective plasma pro teins indicate that these parameters may be helpful in evaluating surgical patients postoperativcly.…”

Section: Discussionmentioning

confidence: 59%

“…No positive cor relation was observed between plasma ceru loplasmin and C-reactive protein concentra tion [17], C-reactive protein showed the highest plasma concentrations up to 3 days after operation, and no further increase during septicemia [4]. Thus, C-rcactive protein did not allow discrimination between the differ ent groups of patients at the onset of the infection and during the course of septicemia, whereas plasma E-ct|Pl levels more specifi cally reflect both the onset and the severity of the postoperative infection than C-reactive protein [4,12]. Plasma C-reactivc protein levels decreased rapidly 3-5 days after opera tion in the present study.…”

Section: Discussionmentioning

confidence: 99%

Plasma Proteinases, Proteinase Inhibitors and Other Selective Plasma Proteins following Aortofemoral Bypass Operation

Hörl¹,

Sperling²,

Mayer³

et al. 1986

Eur Surg Res

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Monitoring of plasma proteinases, proteinase inhibitors and other selective plasma proteins was evaluated in patients undergoing Y-graft aortofemoral bypass operation. Fast-reacting acute-phase proteins (C-reactive protein, antichymotrypsin, α₁-acid glycoprotein) and slow-reacting proteins (haptoglobin, α₁-antitrypsin) increased significantly 48–120 h after operation. By contrast, no significant increase was found between plasma ceruloplasmin levels before clamping and after declamping. Activity and concentration of α₂-macroglobulin decreased postoperatively and remained significantly lowered throughout the observation period. Plasma levels of granulocyte elastase were elevated significantly 1 h after declamping, whereas trypsin-binding capacity decreased immediately after the release of the clamp. Aprotinin pretreatment caused higher trypsin-binding capacity of the plasma, significantly lower ‘unspecific’ proteolytic (azocasein-hydrolyzing) activity and significantly lower non-TCA precipitable low molecular weight plasma protein concentration. Our results confirm the data of several authors that monitoring of plasma proteinases, proteinase inhibitors and other selective plasma proteins may be helpful in evaluating surgical patients postoperatively.

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“…Because of its occurrence in all blood cells (5.8 U/10 9 platelets, 142 U/10 9 mononuclear cells, 140 U/10 9 granulocytes, 4.1 U/10 9 erythrocytes) (27)), with a resulting blood cell/plasma ratio of about 360, lactate dehydrogenase can serve as a general cell injury marker. oti-Proteinase inhibitor and a 2 -macroglobulin are the two major plasma antiproteinases capable of inactivating granulocyte elastase; cxi-proteinase inhibitor additionally acts as acute-phase protein (28). Considering the results for complexed elastase, it is not surprising that these antiproteinases did not increase.…”

Section: Discussionmentioning

confidence: 99%

On the Biocompatibility of IBM 2997 Continuous Flow Plateletapheresis

Lindena¹,

Burkhardt²,

Aulmann³

1990

Clinical Chemistry and Laboratory Medicine

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Summary:During the procedure of centrifugation cytapheresis donors occasionally experience adverse clincial reactions. We evaluated the possibility of whether activation of granulocytes and their subsequent release reactions, which may have been triggered by this extracorporeal circuit, were responsible for these adverse effects. Six blood samples were obtained during various set intervals during plateletapheresis. Of these, four samples were taken directly from each donor. The remaining two were drawn from the efferent lines, i.e. those which return blood from the cytapheresis machine back to the donor. Reactive oxygen species produced by granulocytes were monitored by chemiluminescence using microamounts of whole blood or isolated granulocytes. Furthermore, secreted granulocyte products such as neutral proteinase elastase, present in plasma in a complex with oti-proteinase inhibitor (complexed elastase), and lysosomal -glucuronidase were examined. A complete blood cell count, as well as values of haemoglobin, haematocrit, lactate dehydrogenase, protein, albumin and proteinase inhibitors such as oc 2 -macroglobulin and αϊ-proteinase inhibitor were also determined. Complexed elastase increased from a preapheresis value of about 140 μg/l to about 180 μg/l at the end of the cytapheresis. All other clinical chemical and cytological values were 8 to 12 percent lower than preapheresis values, which can be attributed to inherent plasma volume expansion. Reduced chemiluminescence was observed upon stimulation of phagocytes in the whole blood assay (about 700 counts/min χ ΙΟ 3 χ 50000 cells vs. about 600 counts/min χ ΙΟ 3 χ 50000 cells). This decrease was also seen with stimulated granulocytes (about 5800 counts/min χ ΙΟ 3 χ 50000 cells vs. about 4500 counts/min χ ΙΟ 3 χ 50000 cells). Unstimulated granulocytes, on the other hand, showed an increased native chemiluminescence. These data do not, however, indicate a cytapheresis mediated activation of the oxidative metabolism of granulocytes. Concomitant discharge of proteolytic enzymes remains, therefore, of no clinical importance.

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Proteinases and their Inhibitors in Septicemia - Basic Concepts and Clinical Implications

Cited by 53 publications

References 7 publications

Matrix Metalloproteinases Collagenase-2, Macrophage Elastase, Collagenase-3, and Membrane Type 1-Matrix Metalloproteinase Impair Clotting by Degradation of Fibrinogen and Factor XII

Matrix Metalloproteinases Collagenase-2, Macrophage Elastase, Collagenase-3, and Membrane Type 1-Matrix Metalloproteinase Impair Clotting by Degradation of Fibrinogen and Factor XII

Plasma Proteinases, Proteinase Inhibitors and Other Selective Plasma Proteins following Aortofemoral Bypass Operation

On the Biocompatibility of IBM 2997 Continuous Flow Plateletapheresis

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