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J Allergy Clin Immunol. 2015 Feb;135(2):477-87. doi: 10.1016/j.jaci.2014.07.003. Epub 2014 Aug 13.

Eosinophil-dependent skin innervation and itching following contact toxicant exposure in mice.

Author information

1
Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic in Arizona, Scottsdale, Ariz. Electronic address: jjlee@mayo.edu.
2
Division of Hematology and Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic in Arizona, Scottsdale, Ariz.
3
Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic in Arizona, Scottsdale, Ariz.
4
Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Ore.
5
Media Support Services, Mayo Clinic in Arizona, Scottsdale, Ariz.
6
Department of Dermatology, Mayo Clinic in Arizona, Scottsdale, Ariz.
7
Brophy College Preparatory, Department of Science, Phoenix, Ariz.
8
Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Ore.

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.

KEYWORDS:

Contact hypersensitivity; degranulation; eosinophil-deficient; sensory nerve

PMID:
25129680
PMCID:
PMC4464693
DOI:
10.1016/j.jaci.2014.07.003
[Indexed for MEDLINE]
Free PMC Article

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