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

Abstract

The mechanism of penicillin immediate hypersensitivity reactions has not been completely elucidated. These reactions are generally considered to be mediated by IgE, but penicillin-specific IgE could not be detected in most cases. This study demonstrated that penicillin was able to cause vascular hyperpermeability in a mouse model mimicking clinical symptoms of penicillin immediate hypersensitivity reactions. The first exposure to penicillin also induced immediate edema and exudative reactions in ears and lungs of mice in a dose-dependent manner. Vasodilation was noted in microvessels in ears. These reactions were unlikely to be immune-mediated reactions, because no penicillin-specific IgE was produced. Furthermore, penicillin treatment directly elicited rapid histamine release. Penicillin also led to F-actin reorganization in human umbilical vein endothelial cells and increased the permeability of the endothelial monolayer. Activation of the RhoA/ROCK signaling pathway was observed in ears and lungs of mice and in endothelial cells after treatment with penicillin. Both an anti-histamine agent and a ROCK inhibitor attenuated penicillin immediate hypersensitivity reactions in mice. This study presents a novel mechanism of penicillin immediate hypersensitivity reactions and suggests a potential preventive approach against these reactions.

• Authors: Jiayin Han, Yan Yi, Chunying Li, Yushi Zhang, Lianmei Wang, Yong Zhao, Chen Pan, Aihua Liang
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 33192 (09 13 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27619816 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Penicillins
• rho-Associated Kinases
• rhoA GTP-Binding Protein

Topics

• Animals
• Cell Line, Tumor
• Cells, Cultured
• Ear (blood supply)
• Histamine Release (immunology)
• Human Umbilical Vein Endothelial Cells (immunology, metabolism)
• Humans
• Hypersensitivity, Immediate (immunology, metabolism)
• Lung (immunology, metabolism)
• Male
• Mice, Inbred ICR
• Microvessels (immunology, metabolism)
• Penicillins (immunology)
• Vasodilation (immunology)
• rho-Associated Kinases (immunology, metabolism)
• rhoA GTP-Binding Protein (immunology, metabolism)