Complement-Dependent Accumulation and Degradation of Platelets in the Lung and Liver Induced by Injection of Lipopolysaccharides

Shibazaki, Masahiko; Kawabata, Yoshihiro; Yokochi, Takashi; Nishida, Akira; Takada, Haruhiko; Endo, Yasuo

doi:10.1128/iai.67.10.5186-5191.1999

Cited by 68 publications

(45 citation statements)

References 31 publications

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“…Complement activation has been shown to cause thrombocytopenia in two ways. One is through a direct degradation of platelets [22]. The other is associated with a downstream effect and the accumulation of some cytokines, like TNF-a, which are associated, in their own right, with a rapid decline in platelets count [23].…”

Section: Discussionmentioning

confidence: 99%

Rituximab‐associated acute thrombocytopenia: An under‐diagnosed phenomenon

et al. 2009

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Acute infusion reactions are the most common documented adverse reactions reported with rituximab, with overt cytokine release syndrome, and hematological adverse events being much rarer. The clinical course of a patient with mantle cell lymphoma, who developed acute thrombocytopenia and leukopenia following rituximab administration, is described and the literature reviewed. Serum complement and the levels of three cytokines-TNF-a, IL-6, and IL-1, were measured 2 days after the infusion of rituximab by using ELISA assay. Drug-dependent antibodies against platelets were evaluated by two procedures as follows: an immunofluorescence test applying flow cytometry and Monoclonal Antibody Immobilization of Platelet Antigen (MAIPA). Serum levels of TNF-a were significantly increased compared with normal, whereas those of IL-6 and IL-1 were not increased significantly. Flow cytometry assay and the MAIPA assay failed to detect rituximab-dependent antibodies against platelets. Complement levels were decreased compared with normal. Literature search yielded 10 publications reporting on another 15 patients. The most common type of lymphoma was mantle cell lymphoma, six patients had bone marrow involvement, and 10 patients had splenomegaly. In 10 patients, acute cytopenia was preceded by cytokine release syndrome or infusion-related symptoms. Usually, thrombocytopenia was not associated with bleeding manifestations. Thrombocytopenia was the most commonly acute cytopenia reported. The postulated pathogenesis is associated with cytokine release syndrome and complement activation. Patients with potential risk factors like splenomegaly and bone marrow involvement, who develop clinical manifestations compatible with cytokine release syndrome, should be closely monitored for rituximab-associated cytopenia. Am. J. Hematol. 84:247-250, 2009. V

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Section: Discussionmentioning

confidence: 99%

Rituximab‐associated acute thrombocytopenia: An under‐diagnosed phenomenon

et al. 2009

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“…We earlier proposed that the lectin pathway that forms C3 convertase from C4 and C2 may be involved in the LPS-induced accumulation of platelets in the lung, while the pathway from C5 to C9 is involved in the subsequent platelet destruction and rapid shock [9,10]. Interestingly, Kroes et al [22] reported that both GL and GA inhibit human complement C2 in vitro, while Fujisawa et al [23] found that GL inhibits human C5 or a later stage of the complement cascade in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…Upon recognition of pathogens, mannosebinding lectin (MBL) and ficolins trigger the activation of the lectin pathway through MBL-associated serine proteases (MASPs) [35]. We have shown that activation of the lectin pathway is involved in the LPS-induced activation of platelets [9,10]. MASP-1 has thrombin-like activity [36] and thrombin is also a serine protease.…”

Section: Discussionmentioning

confidence: 99%

“…Using 5-hydroxytryptamine (5HT) as a marker for platelets, we have recently demonstrated that within a few minutes of an intravenous injection of lipopolysaccharide (LPS) into mice, platelets accumulate in the lung and liver (particularly in the lung) [8]. At lower doses of LPS, these platelets soon return to the circulation, but at higher doses they are broken down, with their large-scale breakdown inducing lethal shock [9,10]. This response (the magnitude of which depends on the strain of mouse, the structure of the LPS, and its dose) is induced via an activation of the complement system [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…At lower doses of LPS, these platelets soon return to the circulation, but at higher doses they are broken down, with their large-scale breakdown inducing lethal shock [9,10]. This response (the magnitude of which depends on the strain of mouse, the structure of the LPS, and its dose) is induced via an activation of the complement system [9,10]. Thus, the rapid shock induced by LPS differs from the well-known bendotoxin shockQ seen in mice in that in the latter type, shock signs appear 2-3 h or more later, with death occurring several hours or more later [11].…”

Section: Introductionmentioning

confidence: 99%

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Critical roles of platelets in lipopolysaccharide-induced lethality: effects of glycyrrhizin and possible strategy for acute respiratory distress syndrome

Ohtaki

Kai³

et al. 2005

International Immunopharmacology

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Within a few minutes of an intravenous injection of a lipopolysaccharide (LPS) into mice, platelets accumulate, largely in the lung. At higher doses, LPS induces rapid shock (within 10 min), leading to death within 1 h. This type of shock differs from so-called endotoxin shock, in which shock signs and death occur several hours or more later. Here, we found that platelet depletion (by a monoclonal anti-platelet antibody) prevented LPS-induced rapid shock, but increased delayed lethality. In Japan, glycyrrhizin (GL), a compound isolated from licorice, is daily and slowly infused intravenously into chronic hepatitis C patients. A single bolus intravenous injection into mice of GL (200 mg/kg or less) shortly before (or simultaneously with) LPS injection reduced the pulmonary platelet accumulation and the severity of the rapid shock, and prevented death in both the early and later periods. GL itself, at 400 mg/kg, produced no detectable abnormalities in the appearance or activity of mice. Intraperitoneal injection of aspirin or dexamethasone had only marginal effects on LPS-induced platelet responses and lethality. These results suggest that platelets play important roles in the development of both the rapid and delayed types of shock induced by LPS. Although the mechanism by which GL suppresses platelet responses and delayed lethality remains to be clarified, GL might provide a strategy for alleviating the acute respiratory distress syndrome seen in sepsis. Our results may also support the proposal by Cinatl et al. [Cinatl J, Morgenstern B, Bauer G, Chandra P, Ravenau H, Doerr HW. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet 2003; 361: 2045-6.] that GL may be an effective drug against severe acute respiratory syndrome.

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Paeoniflorin alleviates lipopolysaccharide‐induced disseminated intravascular coagulation by inhibiting inflammation and coagulation activation

Fang

et al. 2020

Drug Development Research

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Lipopolysaccharide (LPS) is a toxic component of the outer membrane of gram-negative bacteria that can activate the blood coagulation system, leading to disseminated intravascular coagulation (DIC). DIC is a syndrome characterized by thromboembolism and multiple organ failure. Herein, the beneficial effect of paeoniflorin (PF) on the alleviation of LPS-induced DIC was investigated with an experimental DIC mouse model. Briefly, mice were randomly divided into the following six groups: (1) control; (2) LPS; (3) heparin;(4) low-PF treatment; (5) medium-PF treatment; and (6) high-PF treatment. The histological morphology of the liver and kidney was observed, and the coagulation indicators (such as prothrombin time), function indicators (such as alanine transferase), and inflammatory factors (such as TNF-α) were detected. Additionally, an in vitro cell inflammation model using RAW 264.7 murine macrophages was established. Activation of the nuclear factor kappa B (NF-κB) signaling pathway and tumor necrosis factor-α (TNF-α) were determined by western blotting. Based on our findings, PF could significantly improve the histological morphology of the liver and kidney, indicating that PF protects the liver and kidney against damage induced by LPS. Additionally, PF improved the function and coagulation indicators and reduced the production of inflammatory factors. In vitro, PF inhibited the expression of TNF-α by suppressing NF-κB signaling pathway activation.Collectively, our findings support the hypothesis that PF has anti-inflammatory and anticoagulation effects for the alleviation of LPS-induced DIC. PF is thus a potential cotreatment option for DIC. K E Y W O R D S disseminated intravascular coagulation (DIC), heparin, lipopolysaccharide (LPS), paeoniflorin (PF), tumor necrosis factor-α (TNF-α)

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Complement-Dependent Accumulation and Degradation of Platelets in the Lung and Liver Induced by Injection of Lipopolysaccharides

Cited by 68 publications

References 31 publications

Rituximab‐associated acute thrombocytopenia: An under‐diagnosed phenomenon

Rituximab‐associated acute thrombocytopenia: An under‐diagnosed phenomenon

Critical roles of platelets in lipopolysaccharide-induced lethality: effects of glycyrrhizin and possible strategy for acute respiratory distress syndrome

Paeoniflorin alleviates lipopolysaccharide‐induced disseminated intravascular coagulation by inhibiting inflammation and coagulation activation

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