Evidence for regulation of endothelial plasminogen-activating system by polymorphonuclear leukocyte elastase

Gilboa, Nisan; Neumann, Paul; Gutmann, Joseph; Vecchio, P. J. Del; Gudewicz, Paul W.

doi:10.1016/0049-3848(89)90216-8

Cited by 12 publications

(3 citation statements)

References 12 publications

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“…Production of superoxide anion was determined by the reduction of ferricytochrome C (Type 111, horse heart, Sigma) (Perlman et al, 1987). Elastase release was determined by the method of Gilboa et al (1989).…”

Section: Reagentsmentioning

confidence: 99%

Tumor necrosis factor enhances the neutrophil‐dependent increase in endothelial permeability

Gibbs

Lai

Malik

1990

Journal Cellular Physiology

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We examined the effect of tumor necrosis factor alpha (TNF alpha) on the increase in pulmonary microvascular endothelial monolayer permeability induced by activated neutrophils (PMN). Layering of PMN onto endothelial monolayers followed by activation of PMN with phorbol 12-myristate 13-acetate (PMA) increased 125I-albumin clearance rate across the monolayers. Pretreatment of endothelial monolayers for 6 hr with TNF alpha (200 U/ml) potentiated the PMN-dependent increase in endothelial permeability, whereas 1 hr or 6 hr pretreatment of endothelial monolayers with 200 U/ml and 100 U/ml, respectively, TNF alpha did not enhance the response. Adherence of PMN to the endothelial cells was increased at 1 and 6 hr after TNF alpha (200 U/ml) treatment, but the adherence response was markedly greater following 6 hr of TNF alpha. The TNF alpha treatment of endothelial cells did not enhance neutrophil activation responses to PMA. Pretreatment of PMN with IB4, a MAb to the CD18 integrin, the common beta subunit of the adhesion proteins LFA-1, Mac-1, and p150,95 of PMN, reduced the increases in PMN adherence and the endothelial monolayer permeability induced by the 6 hr TNF alpha treatment. In contrast, pretreatment of PMN with OKM-1, a MAb to the CD11b epitope (alpha-subunit), had no effect on the adherence and the potentiation of the increase in permeability. The potentiation of the PMN-dependent permeability increase and enhanced endothelial adhesivity at 6 hr after TNF alpha priming of endothelial cells was dependent on protein synthesis. The results indicate that protein synthesis-dependent expression of an endothelial ligand for CD18 and resultant endothelial hyperadhesiveness potentiates the PMN-mediated increase in endothelial permeability after TNF alpha activation of endothelial cells. The priming of endothelial cells by TNF alpha may be a critical step in the mediation of endothelial injury.

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Section: Reagentsmentioning

confidence: 99%

Tumor necrosis factor enhances the neutrophil‐dependent increase in endothelial permeability

Gibbs

Lai

Malik

1990

Journal Cellular Physiology

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“…For exam ple, plasminogen activators, sometimes u-PA, may be generated by leukaemic cells and may induce excessive fibrinolytic activity in the cir culation on occasion, in acute promyelocytic leukaemia. Neutral pro teases such as elastase and cathepsin G may be released in the course of septicaemia; these are capable of degrading several plasma proteins (14,15) and may directly damage the endothelium. In in vitro studies activated polymorphonuclear leucocytes are reported to impair the fibrinolytic system in cultured bovine endothelial cells (16), but the mechanism by which leucocytes influence fibrinolytic inhibition is quite unknown.…”

Section: Introductionmentioning

confidence: 99%

Inhibitors of Plasminogen Activator in Neutrophils and Mononuclear Cells from Septic Patients

Haj

Robbie

Adey³

et al. 1995

Thromb Haemost

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SummaryLeucocytes, both polymorphs and mononuclear cells, play a variety of roles in the evolution of human response to sepsis, both local and generalised. In this study, inhibitors of plasminogen activator were measured in leucocytes from normal and septic patients. Plasminogen activator inhibitor-1 (PAI-1) was identified in polymorphs from normal individuals and levels rose significantly in polymorphs from septic patients: neutrophils from normal subjects did not contain PAI-2 but this protein was detectable in significant quantities in polymorph preparations from septic patients. In contrast, mononuclear cells from normal and septic patients contained no detectable quantities of PAI-1. Significant amounts of PAI-2 were present in normal mononuclear cells, and the levels rose significantly in monocytes from septic patients. PAI-2 is thus here identified in human subjects, distinct from those with pregnancy or malignancy, as playing a role in a pathological process. The increased levels of both inhibitors produced by leucocytes may clearly contribute directly to the persistence of fibrin, a characteristic feature of the response to infection, local or general; they may thus participate in successful localisation of infections (abscess formation etc.) and in the evolution of the major systemic complications of disseminated sepsis characterised by microvascular occlusion by fibrin such as renal failure, shock lung or digital ischaemia.

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“…In this connection collagé nases [15,16] and u-PA [21,22] are sus pected. Collagénases and u-PA are secreted as proenzymes, and various active enzymes [23], including leukocyte elastase [24], cathepsin B [25] and plasmin [11,21], are suggested to be involved in their activation. Collagénases [ 15,16,18] and enzymes of pericellular proteoly sis (u-PA, plasmin) [ 11,21,23,26] have been studied extensively in alkali-burned cornea.…”

Section: Leukocyte Elastase Activity In Rabbit Comeamentioning

confidence: 99%

Histochemical Study of Leukocyte Elastase Activity in Alkali-Burned Rabbit Cornea

Čejková

1997

Ophthalmic Res

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In order to contribute to a better understanding of the role of leukocyte elastase in corneal melting after a severe alkali burn, the in situ appearance and activity of this enzyme in the rabbit cornea was examined. For this reason, a histochemical approach using cryostat sections on membranes and a gel incubation medium with the very sensitive substrate Mu-Ala-Ala-Pro-Val-7-amino-4-trifluoromethylcoumarin (Enzyme Systems Products, Livermore, Calif., USA) was employed. In contrast to the normal rabbit cornea where leukocyte elastase activity was absent, in alkali-burned cornea a high enzyme activity in inflammatory cells (particularly polymorphonuclear leukocytes) was present. The extracellular release of leukocyte elastase into the substantia propria of the corneal stroma was associated with disintegration of the corneal stroma and the appearance of corneal ulcers. These results show that leukocyte elastase is associated with corneal destruction after a severe alkali burn.

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Evidence for regulation of endothelial plasminogen-activating system by polymorphonuclear leukocyte elastase

Cited by 12 publications

References 12 publications

Tumor necrosis factor enhances the neutrophil‐dependent increase in endothelial permeability

Tumor necrosis factor enhances the neutrophil‐dependent increase in endothelial permeability

Inhibitors of Plasminogen Activator in Neutrophils and Mononuclear Cells from Septic Patients

Histochemical Study of Leukocyte Elastase Activity in Alkali-Burned Rabbit Cornea

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