Involvement of Histamine and RhoA/ROCK in Penicillin Immediate Hypersensitivity Reactions.
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.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China.
Jiayin
J
Han
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China.
Yan
Y
Yi
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China.
Chunying
C
Li
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China.
Yushi
Y
Zhang
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China.
Lianmei
L
Wang
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China.
Yong
Y
Zhao
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China.
Chen
C
Pan
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China.
Aihua
A
Liang
D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004423:Ear / Q000098:blood supply; D006636:Histamine Release / Q000276:immunology*; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008297:Male; D008813:Mice, Inbred ICR; D055806:Microvessels / Q000276:immunology / Q000378:metabolism; D010406:Penicillins / Q000276:immunology*; D014664:Vasodilation / Q000276:immunology; D054460:rho-Associated Kinases / Q000276:immunology* / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000276:immunology* / Q000378:metabolism
D010406:Penicillins; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein