Eosinophil-dependent skin innervation and itching following contact toxicant exposure in mice - 05/02/15
Abstract |
Background |
Contact toxicant reactions are accompanied by localized skin inflammation and concomitant increases in site-specific itch responses. The role(s) of eosinophils in these reactions is poorly understood. However, previous studies have suggested that localized eosinophil-nerve interactions at sites of inflammation significantly alter tissue innervation.
Objective |
To define a potential mechanistic link between eosinophils and neurosensory responses in the skin leading to itching.
Methods |
BALB/cJ mice were exposed to different contact toxicants, identifying trimellitic anhydride (TMA) for further study on the basis of inducing a robust eosinophilia accompanied by degranulation. Subsequent studies using TMA were performed with wild type versus eosinophil-deficient PHIL mice, assessing edematous responses and remodeling events such as sensory nerve innervation of the skin and induced pathophysiological responses (ie, itching).
Results |
Exposure to TMA, but not dinitrofluorobenzene, resulted in a robust eosinophil skin infiltrate accompanied by significant levels of degranulation. Follow-up studies using TMA with wild type versus eosinophil-deficient PHIL mice showed that the induced edematous responses and histopathology were, in part, causatively linked with the presence of eosinophils. Significantly, these data also demonstrated that eosinophil-mediated events correlated with a significant increase in substance P content of the cutaneous nerves and an accompanying increase in itching, both of which were abolished in the absence of eosinophils.
Conclusions |
Eosinophil-mediated events following TMA contact toxicant reactions increase skin sensory nerve substance P and, in turn, increase itching responses. Thus, eosinophil-nerve interactions provide a potential mechanistic link between eosinophil-mediated events and neurosensory responses following exposure to some contact toxicants.
Le texte complet de cet article est disponible en PDF.Key words : Contact hypersensitivity, eosinophil-deficient, sensory nerve, degranulation
Abbreviations used : DNCB, DNFB, EAI, EPX-mAb, PGP 9.5, PHIL, TMA
Plan
The performance of these studies, including data analysis and manuscript preparation, was supported by resources from the Mayo Foundation and a grant from the United States National Institutes of Health (NIH; to J.J.L. [HL065228, RR0109709], to N.A.L. [HL058723], to D.B.J. [HL113023], to A.D.F. [ES017592 and ES014601] and to J.J.L. and D.B.J. [AR061567]). These funding sources had no involvement in study design, data collection (including analysis and interpretation), the writing of the manuscript, or the decision to submit for publication. |
|
Disclosure of potential conflict of interest: J. J. Lee has received research support from the National Institutes of Health, consultancy fees from Amgen, payment for development of educational presentations from Jackson Laboratory, and travel support for invited seminars. C. A. Protheroe, H. Luo, S. I. Ochkur, K. R. Zellner, M. V. Dahl, O. Connelly, A. D. Fryer, N. W. Jacoby, D. B. Jacoby, and N. A. Lee have received research support from the National Institutes of Health. M. L. Vega has received research support from the National Institutes of Health and consultancy fees from Amgen. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 135 - N° 2
P. 477 - février 2015 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?