Mechanism of Anaphylactic Death in the Mouse

Muñoz, J.; Bergman, R. K.

doi:10.1038/205199b0

Cited by 39 publications

(28 citation statements)

References 2 publications

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“…Histamine has pratically no effect on mouse smooth muscle, but anaphylaxis in mice is not dependent on smooth muscle spasms on specific regions of the organism, as it may occur in other animal species (1, 2). On the other hand, mouse skin reacts with plasma leakage to the injection of rather low doses of histamine (28), and there is convincing evidence that the severity of anaphylaxis in mice is correlated with hematocrit variations (16,17,18) and death probably results from hypovolemic circulatory failure.…”

Section: Discussionmentioning

confidence: 99%

Histamine Release in vivo during Anaphylaxis in Mice

Vaz¹,

Iff²,

Peixoto³

1966

Int Arch Allergy Immunol

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Section: Discussionmentioning

confidence: 99%

Histamine Release in vivo during Anaphylaxis in Mice

Vaz¹,

Iff²,

Peixoto³

1966

Int Arch Allergy Immunol

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“…Studies with mouse models demonstrate two pathways of systemic anaphylaxis: a classic pathway mediated by IgE, FcgRI, mast cells, histamine, and plateletactivating factor (PAF), and an alternative pathway mediated by IgG, FcgRIII, macrophages, and PAF (1). PAF is a major mediator in the induction of plasma extravasation by promoting vasodilatation and increasing vascular permeability, the most important contributor to fatal reactions in murine anaphylaxis (2). Such PAFmediated effects have been reported to be associated with NO (3-5), a major endogenous regulator of vascular tone.…”

mentioning

confidence: 99%

Protein Kinase CK2/PTEN Pathway Plays a Key Role in Platelet-Activating Factor-Mediated Murine Anaphylactic Shock

Kang

Yoon

Kim

et al. 2011

The Journal of Immunology

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Platelet-activating factor (PAF) is a major mediator in the induction of fatal hypovolemic shock in murine anaphylaxis. This PAF-mediated effect has been reported to be associated with PI3K/Akt-dependent eNOS-derived NO. The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is phosphatidylinositol phosphate phosphatase, which negatively controls PI3K by dephosphorylating the signaling lipid, phosphatidylinositol 3,4,5-triphosphate. In this study, we examined the possible involvement of PTEN in PAF-mediated anaphylactic shock. Induction of anaphylaxis or PAF injection resulted in a rapid decrease in PTEN activity, followed by increases in PI3K activity and phosphorylation of Akt and eNOS. Systemic administration of adenoviruses carrying PTEN cDNA (adenoviral PTEN), but not the control AdLacZ, not only attenuated anaphylactic symptoms, but also reversed anaphylaxis- or PAF-induced changes in PTEN and PI3K activities, as well as phosphorylation of Akt and eNOS. We found that the decreased PTEN activity was associated with PTEN phosphorylation, the latter effect being prevented by the protein kinase CK2 inhibitor, DMAT. DMAT also inhibited anaphylactic symptoms as well as the anaphylaxis- or PAF-mediated PTEN/PI3K/Akt/eNOS signaling cascade. CK2 activity was increased by PAF. The present data provide, as the key mechanism underlying anaphylactic shock, PAF triggers the upstream pathway CK2/PTEN, which ultimately leads to the activation of PI3K/Akt/eNOS. Therefore, CK2/PTEN may be a potent target in the control of anaphylaxis and other many PAF-mediated pathologic conditions.

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“…It is well known that PAF can increase the permeability of blood vessels, resulting in hemoconcentration [7,8]. Therefore, we focused on the possible role of 5-LO metabolites in this study.…”

Section: Resultsmentioning

confidence: 99%

“…An early anaphylactic reaction is thought to be caused by the release of platelet-activating factor (PAF), histamine, serotonin, and many other chemical mediators from mast cells and basophils after antigen-antibody interactions [6]. In murine anaphylaxis, the major cause of fatal reactions is PAF-induced hypovolemic shock [7]. Regarding the downstream pathways beyond PAF-induced early reactions, Choi et al [8] reported that PAF-induced nuclear factor-κB activation and subsequent TNF-α production are essential for the late-phase production of PAF associated with the development of late-phase hypovolemia.…”

Section: Introductionmentioning

confidence: 99%

Glutamine Prevents Late-Phase Anaphylaxis via MAPK Phosphatase 1-Dependent Cytosolic Phospholipase A<sub>2</sub> Deactivation

Kim¹,

Song

Bae

et al. 2016

Int Arch Allergy Immunol

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Background: Cytosolic phospholipase A₂ (cPLA₂) plays a key role in the development of late-phase anaphylaxis. L-Glutamine (Gln), a nonessential amino acid, has anti-inflammatory activity via inhibiting cPLA₂. Methods: We used a penicillin-induced murine model of anaphylaxis, and late-phase anaphylaxis was quantified by measuring the increase in the hematocrit (Ht) value. Various inhibitors, small interfering RNA, and knockout mice were used in inhibition experiments. Phosphorylation and protein expression of cPLA₂, ERK, and MAPK phosphatase 1 (MKP-1) were detected by Western blotting. Results: Leukotriene (LT) B₄ was found to be another potent inducer of late-phase anaphylaxis besides the known mediator platelet-activating-factor (PAF). Gln efficiently prevented late-phase anaphylaxis when it was administered up to 3 h after challenge injection via inhibiting cPLA₂. Inhibition studies indicated that p38 MAPK was the major upstream regulator of cPLA₂. Gln dephosphorylated p38 and cPLA₂ via up-regulating the negative regulator of p38 MAPK, i.e., MKP-1 protein. MKP-1 blockade abrogated all the effects of Gln. Conclusion: Of the cPLA₂ metabolites, PAF and LTB₄ play a key role in the development of late-phase anaphylaxis, and Gln prevents the reaction via MKP-1-dependent deactivation of cPLA₂.

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Mechanism of Anaphylactic Death in the Mouse

Cited by 39 publications

References 2 publications

Histamine Release in vivo during Anaphylaxis in Mice

Histamine Release in vivo during Anaphylaxis in Mice

Protein Kinase CK2/PTEN Pathway Plays a Key Role in Platelet-Activating Factor-Mediated Murine Anaphylactic Shock

Glutamine Prevents Late-Phase Anaphylaxis via MAPK Phosphatase 1-Dependent Cytosolic Phospholipase A<sub>2</sub> Deactivation

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