Involvement of Histamine and RhoA/ROCK in Penicillin Immediate Hypersensitivity Reactions

Han, Jing; Yi, Yan; Li, Chunying; Zhang, Yushi; Wang, Lianmei; Zhao, Yong; Pan, Chen; Liang, Aihua

doi:10.1038/srep33192

Cited by 18 publications

(34 citation statements)

References 55 publications

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“…Fasudil is a potent Rho-associated protein kinase (ROCK) inhibitor [8,9,10,11,12,13] and vasodilator and has been used for the treatment of cerebral vasospasm [9] and many other diseases, such as cancer [14,15], allergy [16] and inflammation [17,18]. The systematic administration of Fasudil was reported protecting mice from experimental autoimmune encephalomyelitis (EAE) and shifting macrophages from M1 to M2 [19].…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization

et al. 2018

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Macrophages play essential roles in the generation and resolution of inflammation. Ischemia-reperfusion injury (IRI) triggers a systemic inflammatory response and leads to cellular injury and organ failure.During surgical procedures of the liver, such as hepatic resection and liver transplantation, IRI leads to the dysfunction of the liver. Rho-associated protein kinase (ROCK) inhibitors were reported protecting the liver from IRI. However, the systematic administration of ROCK inhibitors causes severe hypotension.Here, using Fasudil carried liposomes, we specifically inhibited the ROCK-II expression in Kupffer cells and blood monocytes. Through this macrophage/monocyte specific treatment of Fasudil, we successfully protected the liver from IRI by shifting Kupffer cells/monocytes from M1/classical to M2/patrolling phenotype in the liver and peripheral blood. Our finding provides novel insights into the macrophage/monocyte-specific drug delivery and the treatment of liver IRI.

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Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization

et al. 2018

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“…Penicillins can directly activate the RhoA/Rock signaling pathway, which affects endothelial hyperpermeability. 39 Tannert and coworkers 40 recently reported that histamine was only detected in a few positive intracutaneous penicillin skin test results by microdialysis.…”

Section: Optimal Penicillin Allergy Testing Protocols Based On Reactimentioning

confidence: 99%

Who needs penicillin allergy testing?

Macy¹,

Vyles

2018

Annals of Allergy, Asthma & Immunology

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Credit can now be obtained, free for a limited time, by reading the review article and completing all activity components. Please note the instructions listed below: Review the target audience, learning objectives and all disclosures. Complete the pre-test. Read the article and reflect on all content as to how it may be applicable to your practice. Key Messages All individuals with an unconfirmed penicillin allergy should have their penicillin allergy evaluated and, if appropriate, tested to confirm current hypersensitivity or tolerance. All individuals with a penicillin-associated history of anaphylaxis, rash, gastrointestinal symptoms, headaches, other low-risk symptoms, an unknown history, or a reported family history of penicillin allergy can undergo testing to confirm current tolerance and convince the patient that penicillins can safely be used. The reference standard test to confirm current penicillin class antibiotic hypersensitivity or tolerance is an oral challenge with a therapeutic dose, typically 250 mg for adults, and 1 hour of observation to confirm acute tolerance, followed by 5 days of at home follow-up to confirm the absence of clinically significant T-cell−mediated delayed-onset hypersensitivity. Low-risk individuals, with penicillin reaction histories that are unlikely to be IgE mediated, can safely go to a direct oral amoxicillin challenge with a therapeutic dose to confirm current tolerance. Puncture and intradermal skin testing using only penicilloyl-polylysine, with at least 5 mm of wheal and flare greater than wheal as the criteria for a positive test result, is now sufficient to rule out a high risk of having anaphylaxis during a confirmatory oral amoxicillin challenge. Individuals with positive skin test results should not undergo oral challenges and, like individuals with immediately positive oral challenge results, undergo oral penicillin desensitization if they have a documented infection for which a penicillin is the drug of choice.

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“…The ears of each mouse were shredded and preserved in a tube. Then, 2 mL of formamide was added for EB extraction [15,16]. The high doses of forsythoside A, forsythoside B, and forsythoside E were all designed to be given at 100 mg/kg.…”

Section: Assessment Of Vascular Leakage In Micementioning

confidence: 99%

“…It also inactivates MLC phosphatase and increases endothelial permeability, which is essential for inflammatory responses [8][9][10][11]. Currently, the RhoA/ROCK signaling pathway has been reported to participate in many stimulus-induced endothelial hyperpermeability reactions [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Forsythoside A and Forsythoside B Contribute to Shuanghuanglian Injection-Induced Pseudoallergic Reactions through the RhoA/ROCK Signaling Pathway

Han

Zhang

Pan

et al. 2019

IJMS

Self Cite

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In recent years, hypersensitivity reactions to the Shuanghuanglian injection have attracted broad attention. However, the componential chief culprits inducing the reactions and the underlying mechanisms involved have not been completely defined. In this study, we used a combination of approaches based on the mouse model, human umbilical vein endothelial cell monolayer, real-time cellular monitoring, immunoblot analysis, pharmacological inhibition, and molecular docking. We demonstrated that forsythoside A and forsythoside B contributed to Shuanghuanglian injection-induced pseudoallergic reactions through activation of the RhoA/ROCK signaling pathway. Forsythoside A and forsythoside B could trigger dose-dependent vascular leakage in mice. Moreover, forsythoside A and forsythoside B slightly elicited mast cell degranulation. Correspondingly, treatment with forsythoside A and forsythoside B disrupted the endothelial barrier and augmented the expression of GTP-RhoA, p-MYPT1, and p-MLC2 in a concentration-dependent manner. Additionally, the ROCK inhibitor effectively alleviated forsythoside A/forsythoside B-induced hyperpermeability in both the endothelial cells and mice. Similar responses were not observed in the forsythoside E-treated animals and cells. These differences may be related to the potential of the tested compounds to react with RhoA-GTPγS and form stable interactions. This study innovatively revealed that some forsythosides may cause vascular leakage, and therefore, limiting their contents in injections should be considered.

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Involvement of Histamine and RhoA/ROCK in Penicillin Immediate Hypersensitivity Reactions

Cited by 18 publications

References 55 publications

WITHDRAWN: Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization

WITHDRAWN: Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization

Who needs penicillin allergy testing?

Forsythoside A and Forsythoside B Contribute to Shuanghuanglian Injection-Induced Pseudoallergic Reactions through the RhoA/ROCK Signaling Pathway

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