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Recent advances in disseminated intravascular coagulation: endothelial cells and fibrinolysis in sepsis-induced DIC.

Madoiwa S - J Intensive Care (2015)

Bottom Line: Endothelial cell dysfunction is one of the early signs of systemic inflammation, and it is a trigger of multiple organ failure in sepsis.The marked increase in plasminogen activator inhibitor-1 level causes fibrinolytic shutdown in endotoxemia or sepsis and is one of the most important predictors of multiple organ dysfunction during sepsis-induced disseminated intravascular coagulation (DIC).Leukocytes exhibit the first-line response to microorganisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Laboratory Medicine, Tokyo Saiseikai Central Hospital, 1-14-17, Mita, Minato-ku, Tokyo 108-0073 Japan ; Department of Clinical Laboratory Medicine, Jichi Medical University, 3311-1, Yakushi-ji, Shimotsuke, Tochigi 329-0498 Japan.

ABSTRACT
Endothelial cells are highly active, sensing and responding to signals from extracellular environments. They act as gatekeepers, mediating the recruitment and extravasation of proinflammatory leukocytes to the sites of tissue damage or infection. Endothelial cells participate in fibrinolysis by secreting tissue-type plasminogen activator, which converts plasminogen to active enzyme plasmin through constitutive and regulated pathways. Fibrinolysis systems and inflammation are tightly linked, as both responses are major host defense systems against both healing processes of tissue repair as well as pathogenic microorganisms. Endothelial cell dysfunction is one of the early signs of systemic inflammation, and it is a trigger of multiple organ failure in sepsis. The marked increase in plasminogen activator inhibitor-1 level causes fibrinolytic shutdown in endotoxemia or sepsis and is one of the most important predictors of multiple organ dysfunction during sepsis-induced disseminated intravascular coagulation (DIC). Leukocytes exhibit the first-line response to microorganisms. Leukocyte-derived elastase degrades cross-linked fibrin to yield molecular species distinct from those generated by plasmin. The alternative systems for fibrinolysis that interact with the plasminogen activator-plasmin systems may play crucial roles in the lysis of fibrin clots in sepsis-induced DIC.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of endothelial dysfunction in sepsis. TF, tissue factor; IL-1β, interleukin-1β; TNFα, tumor necrosis factor α; TLR, toll-like receptor; PA-Plm, plasminogen activators-plasmin system; PAI-1, plasminogen activator inhibitor-1.
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Fig2: Schematic representation of endothelial dysfunction in sepsis. TF, tissue factor; IL-1β, interleukin-1β; TNFα, tumor necrosis factor α; TLR, toll-like receptor; PA-Plm, plasminogen activators-plasmin system; PAI-1, plasminogen activator inhibitor-1.

Mentions: The blood coagulation system is drastically altered in sepsis, as the physiological hemostatic balance is shifted toward a procoagulation state. Tissue factor expression is induced in CD14+ monocytes and endothelial cells responding to acute inflammatory mediators (Figure 2). Neutralizing TNF activity by introducing a TNF receptor-IgG fusion protein, or an anti-TNF antibody, did not improve endotoxin-induced coagulopathy [31,32]. By contrast, inhibition of IL-6 completely abrogated tissue factor-dependent thrombin generation, suggesting a major role for endogenous IL-6, and to a lesser extent, IL-1 [33]. Tissue factor from endothelial cells can be shuttled between cells through microparticles derived from activated mononuclear cells [34]. However, the contribution of tissue factor-positive microparticles to the development of DIC has not been determined [35].Figure 2


Recent advances in disseminated intravascular coagulation: endothelial cells and fibrinolysis in sepsis-induced DIC.

Madoiwa S - J Intensive Care (2015)

Schematic representation of endothelial dysfunction in sepsis. TF, tissue factor; IL-1β, interleukin-1β; TNFα, tumor necrosis factor α; TLR, toll-like receptor; PA-Plm, plasminogen activators-plasmin system; PAI-1, plasminogen activator inhibitor-1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940964&req=5

Fig2: Schematic representation of endothelial dysfunction in sepsis. TF, tissue factor; IL-1β, interleukin-1β; TNFα, tumor necrosis factor α; TLR, toll-like receptor; PA-Plm, plasminogen activators-plasmin system; PAI-1, plasminogen activator inhibitor-1.
Mentions: The blood coagulation system is drastically altered in sepsis, as the physiological hemostatic balance is shifted toward a procoagulation state. Tissue factor expression is induced in CD14+ monocytes and endothelial cells responding to acute inflammatory mediators (Figure 2). Neutralizing TNF activity by introducing a TNF receptor-IgG fusion protein, or an anti-TNF antibody, did not improve endotoxin-induced coagulopathy [31,32]. By contrast, inhibition of IL-6 completely abrogated tissue factor-dependent thrombin generation, suggesting a major role for endogenous IL-6, and to a lesser extent, IL-1 [33]. Tissue factor from endothelial cells can be shuttled between cells through microparticles derived from activated mononuclear cells [34]. However, the contribution of tissue factor-positive microparticles to the development of DIC has not been determined [35].Figure 2

Bottom Line: Endothelial cell dysfunction is one of the early signs of systemic inflammation, and it is a trigger of multiple organ failure in sepsis.The marked increase in plasminogen activator inhibitor-1 level causes fibrinolytic shutdown in endotoxemia or sepsis and is one of the most important predictors of multiple organ dysfunction during sepsis-induced disseminated intravascular coagulation (DIC).Leukocytes exhibit the first-line response to microorganisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Laboratory Medicine, Tokyo Saiseikai Central Hospital, 1-14-17, Mita, Minato-ku, Tokyo 108-0073 Japan ; Department of Clinical Laboratory Medicine, Jichi Medical University, 3311-1, Yakushi-ji, Shimotsuke, Tochigi 329-0498 Japan.

ABSTRACT
Endothelial cells are highly active, sensing and responding to signals from extracellular environments. They act as gatekeepers, mediating the recruitment and extravasation of proinflammatory leukocytes to the sites of tissue damage or infection. Endothelial cells participate in fibrinolysis by secreting tissue-type plasminogen activator, which converts plasminogen to active enzyme plasmin through constitutive and regulated pathways. Fibrinolysis systems and inflammation are tightly linked, as both responses are major host defense systems against both healing processes of tissue repair as well as pathogenic microorganisms. Endothelial cell dysfunction is one of the early signs of systemic inflammation, and it is a trigger of multiple organ failure in sepsis. The marked increase in plasminogen activator inhibitor-1 level causes fibrinolytic shutdown in endotoxemia or sepsis and is one of the most important predictors of multiple organ dysfunction during sepsis-induced disseminated intravascular coagulation (DIC). Leukocytes exhibit the first-line response to microorganisms. Leukocyte-derived elastase degrades cross-linked fibrin to yield molecular species distinct from those generated by plasmin. The alternative systems for fibrinolysis that interact with the plasminogen activator-plasmin systems may play crucial roles in the lysis of fibrin clots in sepsis-induced DIC.

No MeSH data available.


Related in: MedlinePlus