Interactions of eosinophil granule proteins with skin

Davis, Mark D.P.; Plager, Douglas A.; George, Terry J.; Weiss, Ellen A.; Gleich, Gerald J.; Leiferman, Kristin M.

doi:10.1016/j.jaci.2003.08.028

Cited by 44 publications

(10 citation statements)

References 47 publications

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“…Despite the frequency of eosinophils identified in dermatologic disease, their roles as an effector cell remains to be fully defined. While dermal injection of ECP and EDN leads to increase vasopermeability, little is known regarding the epidermal response to these degranulation proteins. In this study, we provide evidence of a direct effect of ECP and EDN on keratinocytes, leading to expression of BP‐relevant cytokines, chemokines and a metalloprotease, as well as affecting cell viability and cell‐matrix adhesion.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of pathogenic effects of eosinophil cationic protein and eosinophil‐derived neurotoxin on human keratinocytes

Amber

Chernyavsky

Agnoletti

et al. 2018

Experimental Dermatology

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Cutaneous deposition of eosinophil degranulation proteins is a major feature of eosinophil-rich cutaneous diseases including bullous pemphigoid (BP). We sought to better understand the effect of two of these proteins - eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN), on human keratinocytes using the Het-1A cell line. To evaluate expression of key cytokines and chemokines observed in BP as well as metal metalloprotease 9 (MMP9), we performed qPCR and in-cell Western assays on cells treated with either ECP or EDN. We further evaluated the effect of ECP and EDN on keratinocyte survival, generation of reactive oxygen species (ROS) and apoptosis. Lastly, we assessed ECP and EDN's ability to induce keratinocyte detachment from provisional matrix. Treatment of keratinocytes with ECP and EDN resulted in significant increases in IL-5, eotaxin-1 and CCL5 (RANTES) expression at both mRNA and protein levels, but not IL-17 or IL-31. ECP and EDN also upregulate MMP9 production. Inhibiting MMP9, we confirmed that keratinocyte expression of IL-5, eotaxin-1 and RANTES was independent from MMP9. Both ECP and EDN were cytotoxic to keratinocytes, inducing ROS formation and apoptosis through a mitochondrion-dependent pathway as evidenced by results of terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) and cytochrome c release assays, respectively. ECP but not EDN led to significant keratinocyte detachment from provisional matrix. These findings demonstrate that the pathogenic effects of ECP and EDN in BP may result from their direct action on keratinocytes, and as such may became a target for future therapies in eosinophil-rich cutaneous diseases.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of pathogenic effects of eosinophil cationic protein and eosinophil‐derived neurotoxin on human keratinocytes

Amber

Chernyavsky

Agnoletti

et al. 2018

Experimental Dermatology

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“…Furthermore, i.d. administration of eosinophil granule proteins has also been shown to promote cutaneous vasopermeability [54]. 5.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, i.d. administration of eosinophil granule proteins has also been shown to promote cutaneous vasopermeability [54]. We have elucidated that food allergen-induced cutaneous allergic reactions are associated with CD4 ϩ Th 2 immune responses and are critically regulated by the IL-13/IL-4R ␣ chain pathway.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic analysis of experimental food allergen-induced cutaneous reactions

Prescott

Forbes

Foster

et al. 2006

Journal of Leukocyte Biology

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Individuals with food allergy often present with uritcaria and atopic dermatitis. Indeed, susceptibility to food allergy may predispose to the development of these cutaneous allergic disorders. Recently, we developed a model of food allergy, whereby oral consumption of food [pea Pisum sativum L.; expressing alpha-amylase inhibitor-1 (alphaAI) from the common bean Phaseolus vulgaris L. cv Tendergreen (pea-alphaAI)] promotes a T helper cell type 2 (Th2) inflammatory response and predisposes to cutaneous allergic reactions following subsequent food allergen (alphaAI) exposure. To delineate the kinetics of food allergen-induced cutaneous reactions and examine the inflammatory mechanisms involved in this allergic reaction, we used interleukin (IL)-13-, IL-4 receptor alpha-, and eotaxin-1-deficient mice and performed serum transfer and CD4+ T cell depletion studies. We demonstrate that consumption of pea-alphaAI promotes an alphaAI-specific immunoglobulin G1 (IgG1) and IgE antibody response. Furthermore, we show that subsequent food allergen (alphaAI) challenge in the skin induced an early (3 h)- and late-phase (24 h) cutaneous allergic reaction. The early-phase response was associated with mast cell degranulation and the presence of Ig, whereas the late-phase response was characterized by a lymphoid and eosinophilic infiltrate, which was critically regulated by CD4+ T cells, IL-13, and eotaxin-1. Collectively, these studies demonstrate that food allergy can predispose to cutaneous inflammatory reactions, and these processes are critically regulated by Th2 immune factors.

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“…Moreover, eosinophil granule proteins, which possess cytotoxic activity, are deposited in the skin lesions. Interestingly, Davis et al have shown abundant MBP positive staining in the skin of AD patients even in the absence of eosinophils (Davis et al , 2003). These observations indicate a role for eosinophils in the pathogenesis of AD.…”

Section: Role Of Eosinophils In Diseasementioning

confidence: 99%

Chapter 3 Biology of the Eosinophil

Blanchard

Rothenberg

2009

Advances in Immunology

307

255

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In this review, we aim to put in perspective the biology of a multifunctional leukocyte, the eosinophil, by placing it in the context of innate and adaptive immune responses. Eosinophils have a unique contribution in initiating inflammatory and adaptive responses due to their bidirectional interactions with dendritic cells and T cells, as well as their large panel of secreted cytokines and soluble mediators. The mechanisms and consequences of eosinophil responses in experimental inflammatory models are discussed.

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Interactions of eosinophil granule proteins with skin

Cited by 44 publications

References 47 publications

Mechanisms of pathogenic effects of eosinophil cationic protein and eosinophil‐derived neurotoxin on human keratinocytes

Mechanisms of pathogenic effects of eosinophil cationic protein and eosinophil‐derived neurotoxin on human keratinocytes

Mechanistic analysis of experimental food allergen-induced cutaneous reactions

Chapter 3 Biology of the Eosinophil

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