Contact-mediated stimulation of the monocyte 5-lipoxygenase pathway is enhanced by the presence of platelets

Weide, Ingo; Simmet, Thomas

doi:10.1016/0049-3848(95)91624-t

Cited by 12 publications

(18 citation statements)

References 14 publications

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“…Plasmin(ogen) is not essential for inflammatory cell migration, but it seems to play a critical role in normal functioning, especially bacterial clearance and necrotic tissue removal. In vitro studies have shown that plasmin is a potent and selective stimulus for human peripheral monocytes (33,34). For instance, plasmin has been shown to release macrophage-derived IL-1 and to activate transforming growth factor ␤ (35).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to its function in fibrinolysis, plasmin(ogen) plays a role in degradation of the extracellular matrix (ECM) and in tissue remodeling during many physiologic and pathologic processes, such as wound healing (7), tumor cell invasion, angiogenesis, and rheumatoid arthritis (RA) (8). There is some evidence that plasmin can also induce proinflammatory responses independently of its proteolytic properties (9).…”

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confidence: 99%

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Protective effects of plasmin(ogen) in a mouse model of Staphylococcus aureus–induced arthritis

Guo¹,

Li²,

Hagström³

et al. 2008

Arthritis & Rheumatism

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Objective. To assess the functional roles of plasmin in a murine model of Staphylococcus aureus-induced bacterial arthritis.Methods. Bacterial arthritis was induced in plasminogen-deficient (Plg -/-) and wild-type (Plg ؉/؉ ) littermates by local injection of 1 ؋ 10 6 colony-forming units of S aureus into the knee joints. Human plasminogen was administered to Plg -/-mice on days 0-7 or days 7-14. Antibiotic treatment was administered to Plg -/-mice on days 7-14. Bacteria counts and histologic, immunohistochemical, and Western blot analyses were performed.Results. In Plg ؉/؉ mice, S aureus counts had declined within 2 days, and by day 28 the bacteria had been completely eliminated. However, S aureus was still detectable in all injected joints from Plg -/-mice, and bacteria counts were 27 times higher than the amount injected on day 0. The extent of macrophage and neutrophil recruitment to the infected joints was comparable for Plg ؉/؉ and Plg -/-mice on days 1, 7, and 14. The activation of these inflammatory cells appeared to be impaired in Plg -/-mice, however. Treatment of Plg -/-mice with antibiotic (cloxacillin) resulted in successful killing of the bacteria, but the necrotic tissue remained in the infected joints. When human plasminogen was given intravenously to Plg -/-mice daily for 7 days, bacterial clearance was greatly improved as compared with their untreated counterparts, and the amount of necrotic tissue in the joint cavity was dramatically reduced. The expression of interleukin 6 (IL-6) and IL-10 was higher in Plg ؉/؉ mice than in Plg -/-mice during bacterial arthritis.Conclusion. Our findings indicate that plasmin plays a pluripotent role in protecting against S aureusinduced arthritis by activating inflammatory cells, killing bacteria, removing necrotic tissue, and enhancing cytokine expression.Staphylococcus aureus is the microorganism most frequently associated with bacterial arthritis (1,2), which results in synovial inflammation, cartilage and bone destruction, and eventually, joint deformity (3). The plasminogen activator (PA) system is a general proteolytic system that has been suggested to play an important role in the development of different types of arthritis (4-6). Plasminogen can be activated to the broadspectrum protease plasmin by either of the 2 physiologic PAs, tissue-type PA (tPA) or urokinase-type PA (uPA). In addition to its function in fibrinolysis, plasmin(ogen) plays a role in degradation of the extracellular matrix (ECM) and in tissue remodeling during many physiologic and pathologic processes, such as wound healing (7), tumor cell invasion, angiogenesis, and rheumatoid arthritis (RA) (8). There is some evidence that plasmin can also induce proinflammatory responses independently of its proteolytic properties (9).A number of pathogenic microorganisms have been shown to bind plasminogen (10-12). The subsequent activation of plasminogen to plasmin may contribute to the virulence of these microorganisms (13). However, during bacterial arthritis, plasmin may also be of importance...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Protective effects of plasmin(ogen) in a mouse model of Staphylococcus aureus–induced arthritis

Guo¹,

Li²,

Hagström³

et al. 2008

Arthritis & Rheumatism

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“…Stimulation of human peripheral monocytes with plasmin in vitro induced an upregulation of several inflammatory mediators, including TNF-␣, IL-1␣, IL-1␤, monocyte chemoattractant protein (MCP)-1, and LTB4. [13][14][15] Tranexamic acid attenuated cytokine mRNA expression elicited by plasmin. 13 Plasmin-induced expression of TNF-␣, IL-1␣, and IL-1␤ involved activator protein-1 (AP-1) and nuclear factor-B (NF-B) activation, 13 whereas plasmin-induced monocyte expression of MCP-1 and CD40 was triggered via activation of the p38 MAPK and Janus Kinase/signal transducer and activator of transcription (STAT) signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

“…In vitro, plasmin was demonstrated to stimulate the release of cytokines and other inflammatory mediators by different cell types. [13][14][15][16] Furthermore, plasmin induced cell adhesion and migration in vitro, [17][18][19][20] and studies using plasminogen-deficient mice have provided in vivo evidence for an essential role of the plasminogen system in cell migration toward inflammatory sites. 21,22 Moreover, plasmin can activate the p38 mitogen-activated protein kinase (MAPK) signaling pathway in monocytes, 14,23 and activation of this pathway was recently shown to be of key importance for the inflammatory response to LPS in humans.…”

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confidence: 99%

Inhibition of Plasmin Activity by Tranexamic Acid Does Not Influence Inflammatory Pathways During Human Endotoxemia

Renckens

Weijer

Vos

et al. 2004

ATVB

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Objective-Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems. Methods and Results-To determine the role of early plasmin activity in LPS-induced inflammation in vivo, 16 healthy males received an intravenous bolus injection with LPS (from Escherichia coli, 4 ng/kg) directly preceded by a 30-minute intravenous infusion of tranexamic acid (2 g, nϭ8), a plasmin activation inhibitor, or placebo (nϭ8). LPS injection induced marked increases in the plasma levels of D-dimer and plasmin-␣2-antiplasmin complexes, indicative of plasmin activation and generation, respectively, which were strongly attenuated by tranexamic acid (both PϽ0.01 versus placebo). However, tranexamic acid did not influence LPS-induced coagulation activation, granulocytosis, neutrophil activation (expression of CD11b, CD66b, and L-selectin) or degranulation (plasma concentrations of elastase-␣1-antitrypsin and bactericidal permeability-increasing protein), endothelial cell activation (plasma levels of von Willebrand factor and soluble E-selectin), or cytokine release. Conclusion-These

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“…For instance, plasmin can activate the p38 MAPK signaling pathway in monocytes (7,8), and activation of this pathway was recently shown to be of key importance for the inflammatory response to endotoxin in humans (9,10). Furthermore, in vitro, plasmin was demonstrated to stimulate the release of cytokines and other inflammatory mediators by different cell types (7,(11)(12)(13). Moreover, PAI-1 inhibits uPA, which can enhance LPS-induced cytokine expression in vitro and in vivo (14), and studies using genetically modified mice have implicated uPA as an important regulator of inflammatory responses to bacterial and other stimuli (15,16).…”

mentioning

confidence: 99%

Plasminogen Activator Inhibitor Type-1-Deficient Mice Have an Enhanced IFN-γ Response to Lipopolysaccharide and Staphylococcal Enterotoxin B

Renckens

Pater

Poll

2006

The Journal of Immunology

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Plasminogen activator inhibitor type-1 (PAI-1) is a major inhibitor of fibrinolysis by virtue of its capacity to inhibit urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA). Systemic inflammation is invariably associated with elevated circulating levels of PAI-1, and during human sepsis plasma PAI-1 concentrations predict an unfavorable outcome. Knowledge about the functional role of PAI-1 in a systemic inflammatory response syndrome is highly limited. In this study, we determined the role of endogenous PAI-1 in cytokine release induced by administration of LPS or staphylococcal enterotoxin B (SEB). Both LPS and SEB elicited secretion of PAI-1 into the circulation of normal wild-type (Wt) mice. Relative to Wt mice, PAI-1 gene-deficient (PAI-1−/−) mice demonstrated strongly elevated plasma IFN-γ concentrations after injection of either LPS or SEB. In addition, PAI-1−/− splenocytes released more IFN-γ after incubation with LPS or SEB than Wt splenocytes. Both PAI-1−/− CD4+ and CD8+ T cells produced more IFN-γ upon stimulation with SEB. LPS-induced IFN-γ release in mice deficient for uPA, the uPA receptor, or tPA was not different from IFN-γ release in LPS-treated Wt mice. These results identify a novel function of PAI-1 during systemic inflammation, where endogenous PAI-1 serves to inhibit IFN-γ release by a mechanism that does not depend on its interaction with uPA/uPA receptor or tPA.

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Contact-mediated stimulation of the monocyte 5-lipoxygenase pathway is enhanced by the presence of platelets

Cited by 12 publications

References 14 publications

Protective effects of plasmin(ogen) in a mouse model of Staphylococcus aureus–induced arthritis

Protective effects of plasmin(ogen) in a mouse model of Staphylococcus aureus–induced arthritis

Inhibition of Plasmin Activity by Tranexamic Acid Does Not Influence Inflammatory Pathways During Human Endotoxemia

Plasminogen Activator Inhibitor Type-1-Deficient Mice Have an Enhanced IFN-γ Response to Lipopolysaccharide and Staphylococcal Enterotoxin B

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