Concomitant secretion of prourokinase and of a plasminogen activator-specific inhibitor by cultured human monocytes-macrophages.

Vassalli, Jean‐Dominique; Dayer, Jean‐Michel; Wohlwend, Annelise Isabelle; Belin, Dominique

doi:10.1084/jem.159.6.1653

Cited by 410 publications

(206 citation statements)

References 43 publications

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“…uPA is a pro-HGF convertase (13,29), whose expression is known to be induced in monocytes upon activation (41). As previously described (29), suspensions of freshly prepared mononuclear cells are unable to process 125 I-labeled proHGF in serum-free conditions, while efficient proteolytic cleavage can be detected in adherent monocytes.…”

Section: Activated Monocytes Efficiently Process Pro-hgf To the Maturmentioning

confidence: 95%

Hepatocyte Growth Factor Is a Regulator of Monocyte-Macrophage Function

Galimi

Cottone

Vigna

et al. 2001

The Journal of Immunology

116

106

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Hepatocyte growth factor (HGF) is a potent paracrine mediator of stromal/epithelial interactions, which is secreted as a matrix-associated inactive precursor (pro-HGF) and locally activated by tightly controlled urokinase cleavage. It induces proliferation and motility in epithelial and endothelial cells, and plays a role in physiological and pathological processes involving invasive cell growth, such as angiogenesis and parenchymal regeneration. We now report that HGF induces directional migration and cytokine secretion in human monocytes. Monocyte activation by endotoxin and IL-1β results in the up-regulation of the HGF receptor expression and in the induction of cell-associated pro-HGF convertase activity, thus enhancing cell responsiveness to the factor. Furthermore, we provide evidence for the secretion of biologically active HGF by activated monocytes, implying an autocrine stimulation. Altogether, these data indicate that monocyte function is modulated by HGF in a paracrine/autocrine manner, and provide a new link between stromal environment and mononuclear phagocytes.

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Section: Activated Monocytes Efficiently Process Pro-hgf To the Maturmentioning

confidence: 95%

Hepatocyte Growth Factor Is a Regulator of Monocyte-Macrophage Function

Galimi

Cottone

Vigna

et al. 2001

The Journal of Immunology

116

106

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“…This may be due to the presence of inhibitors of PA which upon fractionation were distributed into separate (most likely soluble) compartments . Such inhibitors have been shown to be present in a number of cells, including macrophages (30) . The presence of inhibitors makes the calculation of enzyme recovery in different steps of fractionation somewhat uncertain.…”

mentioning

confidence: 99%

Human neutrophil plasminogen activator is localized in specific granules and is translocated to the cell surface by exocytosis.

Heiple¹,

Ossowski²

1986

The Journal of Experimental Medicine

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Plasminogen activator (PA)' is produced and secreted by mouse and human monocytes and neutrophils (1-4). A role for the enzyme in cell migration associated with inflammation has been postulated (5). Recently, a specific PA receptor on the surface of monocytes has been described (6, 7). PA bound to this receptor remains active, providing a mechanism through which a cell can concentrate proteolytic activity on its membrane . This finding suggests PA participation in processes requiring direct, local proteolysis.It has been shown that PA activity of macrophages and neutrophils can be modulated by agents such as Con A, PMA, or glucocorticoids (1, 3, 5). In these experiments, long-term effects were studied and the enzyme was measured either in whole cell lysates or in the conditioned medium. In a number of other studies (8-12) involving thymocytes, macrophages, basophils, and several tumor cell lines, the subcellular localization of PA has been examined but no uniform conclusion has been reached, nor was a comparison of subcellular PA distribution in resting and activated states in neutrophils or any other cells attempted.Using a previously published method (13) of neutrophil fractionation, we obtained highly enriched fractions of azurophilic and specific granules and plasma membranes, and we determined PA activity in these fractions. We compared the localization of PA in resting and activated neutrophils.Our results provide evidence that in resting neutrophils most of PA is associated with the specific granule membranes, and upon activation, PA translocates to the plasma membrane, thus equipping the neutrophil with surface-associated proteolytic activity .

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“…These effects may be important in progression of HIV disease because high levels of UK may prevent T or B cell proliferation and/or cytokine production required for effective immune responses, perhaps through proteolytic cleavage of cell surface markers (receptors) and/or cytokines (see above). It is well recognized that healthy human peripheral blood lymphocytes can be co-stimulated by phytohemagglutinin and neutral proteases or serine esterase such as UK [2,23]; in fact, UK alone is slightly mitogenic for healthy cells [8]. However, it is also well recognized that serine proteases can suppress the ability of healthy human blood lymphocytes to respond to phytohemagglutinin.…”

Section: Discussionmentioning

confidence: 99%

“…Urokinase (UK) type plasminogen activator is a serine protease produced by activated human monocytes [1][2][3][4]. Plasminogen activators play important roles in wound healing because they activate plasminogen into plasmin, which in turn breaks down fibrin clots [5].…”

Section: Introductionmentioning

confidence: 99%

Altered levels of urokinase on monocytes and in serum of children with AIDS; effects on lymphocyte activation and surface marker expression

Murali

Wolfe²,

Erber³

et al. 1998

Journal of Leukocyte Biology

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Urokinase (UK) type plasminogen activator is a serine protease produced by activated human monocytes. Despite the well-documented roles played by UK in cell-mediated immunity in healthy humans, the roles played by UK in the derangements of cell-mediated immune responses observed in HIV disease remain largely undefined. In these studies the numbers of peripheral blood lymphocytes and monocytes bearing surface UK (UK ؉ ) as well as serum levels of UK (flow microfluorimetry and ELISA, respectively) were determined in children with AIDS and in healthy HIV-negative children. The effects of exogenous UK on lymphocyte activation (cell cycle analysis using living cells) and surface marker (CD3, CD4, CD8, and CD19) expression (flow microfluorimetry using fixed cells) were also studied. Data are expressed as percent total cells. Numbers of UK ؉ lymphocytes in children with AIDS were similar to those observed in healthy children. In contrast, numbers of UK ؉ peripheral blood monocytes were dramatically decreased (G70%) in the children with AIDS. However, serum levels of UK were increased (nearly threefold) in these children. When lymphocytes from these children were cultured with soluble UK, numbers of cells in S phase of cell cycle appeared suppressed. Incubation of fixed lymphocytes from either a child with AIDS or from a healthy child with exogenous UK appeared to increase numbers of cells expressing CD3. Incubation with UK had no effect on expression of any other surface marker (CD4, CD8, or CD19) using cells from the child with AIDS. In contrast, incubation with UK appeared to decrease (fivefold) numbers of cells expressing CD19 and increase numbers of cells expressing CD4 and CD8 only when fixed lymphocytes from a healthy HIV-negative child were used. The results suggest important roles for UK in regulation of lymphocyte surface markers in general and in CD3-and CD19-dependent lymphocyte activation pathways specifically. Furthermore, these studies add to a widening body of evidence implicating UK dysregulation in the pathogenesis of HIV disease and may point to pharmacological opportunities involving UK to delay or prevent progression of HIV infection into full-blown AIDS.

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Concomitant secretion of prourokinase and of a plasminogen activator-specific inhibitor by cultured human monocytes-macrophages.

Cited by 410 publications

References 43 publications

Hepatocyte Growth Factor Is a Regulator of Monocyte-Macrophage Function

Hepatocyte Growth Factor Is a Regulator of Monocyte-Macrophage Function

Human neutrophil plasminogen activator is localized in specific granules and is translocated to the cell surface by exocytosis.

Altered levels of urokinase on monocytes and in serum of children with AIDS; effects on lymphocyte activation and surface marker expression

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