biostudies-literatureLee JJNCRR NIH HHSNIEHS NIH HHSNHLBI NIH HHSNIAMS NIH HHS477-87https://www.ebi.ac.uk/biostudies/studies/S-EPMC4464693biostudies-literatureUnknown135(2)<h4>Background</h4>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.<h4>Objective</h4>To define a potential mechanistic link between eosinophils and neurosensory responses in the skin leading to itching.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.The Journal of allergy and clinical immunologyEosinophil-dependent skin innervation and itching following contact toxicant exposure in mice.PMC4464693R01 AR061567R01 ES017592RR0109709HL065228ES017592K26 RR019709R01 ES014601R56 HL058723HL058723[HL113023R01 HL113023R01 HL058723R01 HL065228AR061567ES014601F30 HL106930Protheroe CAKloeber JAJacoby NWRaish RJMaizer PLee NALuo HJacoby DBDahl MVMazzolini AScott GDOchkur SIConley ONeely JLLee JJCondjella RMZellner KRPatel YSVega MLFryer ADfalseEosinophil-dependent skin innervation and itching following contact toxicant exposure in mice.<h4>Background</h4>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.<h4>Objective</h4>To define a potential mechanistic link between eosinophils and neurosensory responses in the skin leading to itching.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.2015-01-01T00:00:00Z2015 Feb2026-05-02T05:15:18.153Z2019-03-27T01:53:20ZS-EPMC44646932512968010.1016/j.jaci.2014.07.003