Oxidative Stress: Promoter of Allergic Sensitization to Protease Allergens?

Leonie Van Rijt,Lara Utsch,Ronald Van Ree,René Lutter

doi:10.3390/ijms18061112

Leonie Van Rijt, Lara Utsch + Show 2 more

Open Access

https://doi.org/10.3390/ijms18061112

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Abstract

Allergies arise from aberrant T helper type 2 responses to allergens. Several respiratory allergens possess proteolytic activity, which has been recognized to act as an adjuvant for the development of a Th2 response. Allergen source-derived proteases can activate the protease-activated receptor-2, have specific effects on immune cells by cleaving cell membrane-bound regulatory molecules, and can disrupt tight junctions. The protease activity can induce a non-allergen-specific inflammatory response in the airways, which will set the stage for an allergen-specific Th2 response. In this review, we will discuss the evidence for the induction of oxidative stress as an underlying mechanism in Th2 sensitization to proteolytic allergens. We will discuss recent data linking the proteolytic activity of an allergen to its potential to induce oxidative stress and how this can facilitate allergic sensitization. Based on experimental data, we propose that a less proficient anti-oxidant response to allergen-induced oxidative stress contributes to the susceptibility to allergic sensitization. Besides the effect of oxidative stress on the immune response, we will also discuss how oxidative stress can increase the immunogenicity of an allergen by chemical modification.

Highlights

Many airborne allergens, like those from house dust mites (HDM), cockroaches, pollen, cat dander and fungi possess protease activity [1,2]
Most proteolytic allergens belong to the class of serine proteases like trypsin, chymotrypsin and collagenolytic-like
Dual oxidase (DUOX) 1 and 2 are isoforms of NAD(P)H oxidases (NOX) expressed in the airway epithelium and contrary to other NOX, they do not require cytosolic activation or subunit assembly but instead they are directly activated by intracellular Ca2+ [12]

Summary

Introduction

Like those from house dust mites (HDM), cockroaches, pollen, cat dander and fungi possess protease activity [1,2]. Allergen exposure can trigger the release of several chemokines and cytokines, like Granulocyte-macrophage colony-stimulating factor (GM-CSF), by structural or innate immune cells [14,15] and can potentially trigger cytosolic activation of NOX. Dual oxidase (DUOX) 1 and 2 are isoforms of NOX expressed in the airway epithelium and contrary to other NOX, they do not require cytosolic activation or subunit assembly but instead they are directly activated by intracellular Ca2+ [12] Another important source of ROS is XOR. There seems to be a delicate balance between the induced reactive oxygen species by exposure to the allergen, for example by activation of protease activated receptor-2, and the anti-oxidant response by the host. Tohf issruapdeircoaxl ids ed.ismThuitsateraddiinctaol His2Od2 iasnmduotaxtyegdeninsptoonHta2nOe2ouasnlydorobxyygthene ascptoionntaonfeEouCs-lSyOoDr;bXyanththe iancetiooxnidoafsEeCca-SnObDe;aXctainvtahteindeboyxsidevaeseraclapnatbhewaacytisviantecldudbyinsgepvreorateloplyatshiswaanyds TinLcRlu4d, tinrigggperointegoglyesniesraatniodn ToLf uRr4i,c tarciigdg,esruinpgerogxeindeeraatniodnhyodf ruogriecnapceidro,xsiduep.eIrnocxriedaeseadnidnthraycderllougleanr ppreordouxicdtieo.nInocfrseuapserdoxinidtrearceeslulultlsarinptrhoedruecletiaosne oofffsreuepierroonxsidfreomresiuroltns-siunlftuhrecrluelsetaesrse (oVf)ffreeeedirnognFsefnrtoomn rireoanct-isounlfu(Vr Ic)lyuisetledrsin(gVh)yfdeerodxinygl ioFnens.toHnyrderaocxtiyolnli(pVoIp)hyiliiecldpirnogpehrytidersorxeysluilot nins.aHttaycdkrooxnylmleipmobprhainliec lpiproidpseirntieasprreoscueslts icnallaetdtalcipkidonpemroexmidbartaionne gliepniedrsatiinngaanporothceersspoctaelnletdoxliipdiadntp4e-rHoNxiEd.aOtioxnidagteivneersattriensgs parnoovtihdeersptohteecnotnodxiitdioanntfo4-rHthNeEa.cOtivxaidtiaotnivaensdtrnesusclperaorvtirdaenssltohceactioonndoitfiotrnanfoscrrtihpetiaocntifvaacttioorns FanOdXnOu4calenadr Ntrarfn2silnocitaiatitoinngotfhteratnrasncrsicprtipiotniofnacotfokresyFOanXtiOo4xiadnadntNenrfz2yimnietsia. ting the transcription of key antioxidant enzymes

Tissue Damage

Protease Allergens Trigger Reactive Oxygen Species Production in Immune Cells

Oxidative Stress Generation Due to Inadequate Antioxidant Responses

EEffffeecctt ooff OOxxiiddaattiive Stress on Protein Immunogenicity

Summary and Concluding Remarks