Imperial College London
Alternate

DrKenjiWakabayashi

Faculty of Medicine, Department of Surgery & Cancer

Honorary Research Fellow
 
 
 
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Contact

 

+44 (0)20 3315 8023k.wakabayashi

 
 
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Assistant

 

Miss Steffi Klier +44 (0)20 3315 8816

 
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Location

 

G3.41Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@inproceedings{Wakabayashi:2013,
author = {Wakabayashi, K and Wilson, MR and Patel, BV and Morley, PJ and Baycliffe, A and Takata, M},
title = {Inhibition Of TNF Receptor p55 By A Domain Antibody Attenuates Acid-Induced Lung Injury In Mice},
year = {2013}
}
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RIS format (EndNote, RefMan)

TY  - CPAPER
AB  - RationaleTumor necrosis factor (TNF) is strongly implicated in the evolution of acute lung injury (ALI), but its potential as a therapeutic target has been hampered by its complex biology. TNF signals through two cell surface receptors, p55 and p75, which play differential roles in ALI, with p55 promoting injury while p75 opposes this. We have recently shown that selective p55 blockade using novel domain antibody technology attenuates ventilator-induced lung injury (VILI) in mice. To further translate these findings to the bedside, we explored the potential for selective blockade of p55 in a clinically relevant mouse model of acid-induced ALI.MethodsMale C57BL6 mice were pretreated with intranasal administration of either specific domain antibody to p55 (dAb) or non-specific control domain antibody (‘dummy’). Four hours later, the mice were either instrumented for analysis without further instillation (i.e. baseline) or intratracheally challenged with hydrochloric acid (0.1M, 75μl) via an oro-tracheal tube to induce ALI. All acid-challenged animals were instrumented for analysis at 24 hours after acid instillation. Analysis consisted of mice being anesthetized, tracheostomized, and mechanically ventilated in order to evaluate PaO2/FiO2 ratio and respiratory mechanics. The left lung was taken for determining wet/dry ratio and a lunglavage sample was taken from the right lung to measure protein levels and neutrophil counts.ResultsHydrochloric acid instillation in the dummy group resulted in severe ALI, represented by hypoxemia, elastance increase, pulmonary edema and inflammation (Table 1). These mice were also visually very sick, showing considerably reduced locomotion and responsiveness. In contrast, pretreatment with p55 dAb dramatically improved the clinical symptoms, along with significant attenuation in all the physiological markers of lung injury. However, the dAb treatment did not significantly attenuate lung neutrophil recruitment represented b
AU  - Wakabayashi,K
AU  - Wilson,MR
AU  - Patel,BV
AU  - Morley,PJ
AU  - Baycliffe,A
AU  - Takata,M
PY  - 2013///
TI  - Inhibition Of TNF Receptor p55 By A Domain Antibody Attenuates Acid-Induced Lung Injury In Mice
ER  -
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