Pharmacological characterization of anaphylaxis-like shock responses induced in mice by mannan and lipopolysaccharide

Funayama, Hiromi; Huang, Ling; Sato, Tadasu; Ohtaki, Yuko; Asada, Yoshinobu; Yokochi, Takashi; Takada, Haruhiko; Sugawara, Shunji; Endo, Yasuo

doi:10.1016/j.intimp.2009.09.006

Cited by 8 publications

(10 citation statements)

References 58 publications

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“…39,40 Early coagulopathy is also a key component of HS-R. 27 In the present study, mice deficient in TLR4 showed intact platelet function compared to the platelet impairment seen in WT mice when subjected to HS-R, suggesting that HS-R may also modulate platelet function in a TLR4 dependent manner. Similar observations have been reported in sepsis models where LPS induced platelet aggregation was abolished by an anti-TLR4-blocking antibody or TLR4 knockout in mice.…”

Section: Discussionsupporting

confidence: 47%

Toll-Like Receptor 4 Regulates Platelet Function and Contributes to Coagulation Abnormality and Organ Injury in Hemorrhagic Shock and Resuscitation

Ding

Chen

Hoffman

et al. 2014

Circ Cardiovasc Genet

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Background Growing evidence indicates that the presence of TLR4 on platelets is a key regulator of platelet number and function. Platelets exposed to TLR4 agonists may serve to activate other cells such as neutrophils and endothelial cells in sepsis and other inflammatory conditions. The functional significance of platelet TLR4 in hemorrhagic shock, however, remains unexplored. Methods and Results Using thromboelastography and platelet aggregometry, we demonstrate that platelet function is impaired in a mouse model of hemorrhagic shock with resuscitation (HS-R). Further analysis using cellular specific TLR4 deletion in mice revealed that platelet TLR4 is essential for platelet activation and function in HS-R and that platelet TLR4 regulates the development of coagulopathy after hemorrhage and resuscitation. Transfusion of TLR4 negative platelets into mice resulted in protection from coagulopathy and restored platelet function. Additionally, platelet-specific TLR4 knock-out mice were protected from lung and liver injury and exhibited a marked reduction in systemic inflammation as measured by circulating IL-6 following HS-R. Conclusions We demonstrate for the first time that platelet TLR4 is an essential mediator of the inflammatory response as well as platelet activation and function in hemorrhagic shock and resuscitation.

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Section: Discussionsupporting

confidence: 47%

Toll-Like Receptor 4 Regulates Platelet Function and Contributes to Coagulation Abnormality and Organ Injury in Hemorrhagic Shock and Resuscitation

Ding

Chen

Hoffman

et al. 2014

Circ Cardiovasc Genet

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“…[19-20] In anaphylaxis-like shock (ALS) induced by mannan, a component of fungal cell surfaces, severity increases when platelets have been depleted, suggestive that platelets play a role in the recognition and clearance of this pathogen. [16] These results are contrary to LPS- induced ALS, in which platelet depletion attenuated the disease state. [16]…”

Section: Tlrs and Plateletsmentioning

confidence: 95%

“…Coagulation abnormalities are common in severe sepsis and it is possible that the presence of TLRs on platelets could be the link between disseminated intravascular coagulation and sepsis. [15-16] While growing evidence has clearly established the relevance of platelets in inflammation, there is much circumstantial evidence that they are also relevant in the setting of infection. An early study showed that LPS, at high doses, actually inhibited platelet activation.…”

Section: Tlrs and Plateletsmentioning

confidence: 99%

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The role of inflammation in regulating platelet production and function: Toll-like receptors in platelets and megakaryocytes

Beaulieu

Freedman

2010

Thrombosis Research

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Platelets have been extensively studied as hemostatic regulators, stopping uncontrolled flow of blood from an injured vessel and allowing for repair. However, multiple studies have shown that platelets can interact with bacterial proteins, particularly seen during sepsis and inflammation. Immune cells recognize pathogens through Toll-like Receptors (TLRs). These same receptors allow platelets to recognize bacterial proteins and regulate platelet immunity and function. This review examines the TLRs expressed on platelets and megakaryocytes and how these receptors affect the function of these cells. Through TLRs, platelets go beyond hemostatic regulation and play a pivotal role in inflammation and infection.

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“…5B is one of the characteristic events in platelet-dependent systemic anaphylaxis [40]. Platelet depletion by Pm-1 prevents anaphylaxis-like shock being induced in mice by a certain type of LPS [23,41,42]. However, such platelet depletion failed to prevent the lethal effects of LPS plus RB6-8C5 (Table 3), suggesting that platelets are not a major mediator of this type of shock.…”

Section: Neutrophils and Macrophages Are Involved In Shock Induction mentioning

confidence: 99%

Stimulation of Ly-6G on neutrophils in LPS-primed mice induces platelet-activating factor (PAF)-mediated anaphylaxis-like shock

Tanaka

Nagai

Kuroishi

et al. 2011

Journal of Leukocyte Biology

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Previously, two anti-Ly-6G mAb-RB6-8C5 and 1A8-have been used to deplete neutrophils in mice and to clarify their involvement in immune responses. During the course of experiments on neutrophil depletion, we noticed that i.v. injection of RB6-8C5 or 1A8 induced anaphylaxis-like shock in mice pretreated i.v. with LPS. Signs of shock, such as hypothermia, appeared within a few minutes, and the mice died of shock within 20 min of the antibody injection. In vivo experiments, including depletion of various cell types, indicated that neutrophils and macrophages (but not platelets, basophils, or mast cells) are involved in the shock. Experiments using various drugs and gene-targeted mice demonstrated that PAF is the central mediator of the shock. Optimal LPS priming required at least 1 h, and the priming was associated with neutrophil accumulation within pulmonary and hepatic blood vessels. Consistently, following 1A8 injection into LPS-pretreated mice, the mRNA for LysoPAFAT (a PAF biosynthetic enzyme) was markedly up-regulated in neutrophils accumulated in the lung but not in macrophages. These results suggest that (1) stimulation of Ly-6G on LPS-primed neutrophils induces PAF-mediated anaphylaxis-like shock in mice, (2) neutrophils are primed by LPS during and/or after their accumulation in lung and liver to rapidly induce LysoPAFAT, and (3) macrophages may play a pivotal role in the priming phase and/or in the challenge phase by unknown mechanisms. These findings may be related to adult respiratory distress syndrome, although the natural ligand for Ly-6G remains to be identified.

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Pharmacological characterization of anaphylaxis-like shock responses induced in mice by mannan and lipopolysaccharide

Cited by 8 publications

References 58 publications

Toll-Like Receptor 4 Regulates Platelet Function and Contributes to Coagulation Abnormality and Organ Injury in Hemorrhagic Shock and Resuscitation

Toll-Like Receptor 4 Regulates Platelet Function and Contributes to Coagulation Abnormality and Organ Injury in Hemorrhagic Shock and Resuscitation

The role of inflammation in regulating platelet production and function: Toll-like receptors in platelets and megakaryocytes

Stimulation of Ly-6G on neutrophils in LPS-primed mice induces platelet-activating factor (PAF)-mediated anaphylaxis-like shock

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