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

James J. Lee, Cheryl A. Protheroe, Huijun Luo, Sergei I. Ochkur, Gregory D. Scott, Katie R. Zellner, Randall J. Raish, Mark V. Dahl, Miriam L. Vega, Olivia Conley, Rachel M. Condjella, Jake A. Kloeber, Joseph L. Neely, Yash S. Patel, Patty Maizer, Andrew Mazzolini, Allison D. Fryer, Noah W. Jacoby, David B. Jacoby, Nancy A Lee

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)477-487
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Volume135
Issue number2
DOIs
StatePublished - Feb 1 2015

Fingerprint

Pruritus
Eosinophils
Skin
Substance P
Dinitrofluorobenzene
Inflammation
Eosinophilia
trimellitic anhydride

Keywords

  • Contact hypersensitivity
  • degranulation
  • eosinophil-deficient
  • sensory nerve

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Eosinophil-dependent skin innervation and itching following contact toxicant exposure in mice. / Lee, James J.; Protheroe, Cheryl A.; Luo, Huijun; Ochkur, Sergei I.; Scott, Gregory D.; Zellner, Katie R.; Raish, Randall J.; Dahl, Mark V.; Vega, Miriam L.; Conley, Olivia; Condjella, Rachel M.; Kloeber, Jake A.; Neely, Joseph L.; Patel, Yash S.; Maizer, Patty; Mazzolini, Andrew; Fryer, Allison D.; Jacoby, Noah W.; Jacoby, David B.; Lee, Nancy A.

In: Journal of Allergy and Clinical Immunology, Vol. 135, No. 2, 01.02.2015, p. 477-487.

Research output: Contribution to journalArticle

Lee, JJ, Protheroe, CA, Luo, H, Ochkur, SI, Scott, GD, Zellner, KR, Raish, RJ, Dahl, MV, Vega, ML, Conley, O, Condjella, RM, Kloeber, JA, Neely, JL, Patel, YS, Maizer, P, Mazzolini, A, Fryer, AD, Jacoby, NW, Jacoby, DB & Lee, NA 2015, 'Eosinophil-dependent skin innervation and itching following contact toxicant exposure in mice', Journal of Allergy and Clinical Immunology, vol. 135, no. 2, pp. 477-487. https://doi.org/10.1016/j.jaci.2014.07.003
Lee, James J. ; Protheroe, Cheryl A. ; Luo, Huijun ; Ochkur, Sergei I. ; Scott, Gregory D. ; Zellner, Katie R. ; Raish, Randall J. ; Dahl, Mark V. ; Vega, Miriam L. ; Conley, Olivia ; Condjella, Rachel M. ; Kloeber, Jake A. ; Neely, Joseph L. ; Patel, Yash S. ; Maizer, Patty ; Mazzolini, Andrew ; Fryer, Allison D. ; Jacoby, Noah W. ; Jacoby, David B. ; Lee, Nancy A. / Eosinophil-dependent skin innervation and itching following contact toxicant exposure in mice. In: Journal of Allergy and Clinical Immunology. 2015 ; Vol. 135, No. 2. pp. 477-487.
@article{b712095daa3041599d98884740cf176e,
title = "Eosinophil-dependent skin innervation and itching following contact toxicant exposure in mice",
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",
author = "Lee, {James J.} and Protheroe, {Cheryl A.} and Huijun Luo and Ochkur, {Sergei I.} and Scott, {Gregory D.} and Zellner, {Katie R.} and Raish, {Randall J.} and Dahl, {Mark V.} and Vega, {Miriam L.} and Olivia Conley and Condjella, {Rachel M.} and Kloeber, {Jake A.} and Neely, {Joseph L.} and Patel, {Yash S.} and Patty Maizer and Andrew Mazzolini and Fryer, {Allison D.} and Jacoby, {Noah W.} and Jacoby, {David B.} and Lee, {Nancy A}",
year = "2015",
month = "2",
day = "1",
doi = "10.1016/j.jaci.2014.07.003",
language = "English (US)",
volume = "135",
pages = "477--487",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "2",

}

TY - JOUR

T1 - Eosinophil-dependent skin innervation and itching following contact toxicant exposure in mice

AU - Lee, James J.

AU - Protheroe, Cheryl A.

AU - Luo, Huijun

AU - Ochkur, Sergei I.

AU - Scott, Gregory D.

AU - Zellner, Katie R.

AU - Raish, Randall J.

AU - Dahl, Mark V.

AU - Vega, Miriam L.

AU - Conley, Olivia

AU - Condjella, Rachel M.

AU - Kloeber, Jake A.

AU - Neely, Joseph L.

AU - Patel, Yash S.

AU - Maizer, Patty

AU - Mazzolini, Andrew

AU - Fryer, Allison D.

AU - Jacoby, Noah W.

AU - Jacoby, David B.

AU - Lee, Nancy A

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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.

AB - 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.

KW - Contact hypersensitivity

KW - degranulation

KW - eosinophil-deficient

KW - sensory nerve

UR - http://www.scopus.com/inward/record.url?scp=84922378854&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922378854&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2014.07.003

DO - 10.1016/j.jaci.2014.07.003

M3 - Article

C2 - 25129680

AN - SCOPUS:84922378854

VL - 135

SP - 477

EP - 487

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 2

ER -