Toxicology of Contact Hypersensitivity


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Navarro-Tovar, G. An overview on the role of silica-based materials in vaccine development. Scheiblhofer, S. Potential of nanoparticles for allergen-specific immunotherapy - use of silica nanoparticles as vaccination platform. Brandenberger, C. Engineered silica nanoparticles act as adjuvants to enhance allergic airway disease in mice. Han, H. Toxic and adjuvant effects of silica nanoparticles on ovalbumin-induced allergic airway inflammation in mice.

Morris, A. Amine modification of nonporous silica nanoparticles reduces inflammatory response following intratracheal instillation in murine lungs. Parveen, A. Intranasal exposure to silica nanoparticles induces alterations in pro-inflammatory environment of rat brain. Hassankhani, R. In vivo toxicity of orally administrated silicon dioxide nanoparticles in healthy adult mice.

Toda, T. Amorphous nanosilica particles block induction of oral tolerance in mice. Nabeshi, H. Size-dependent cytotoxic effects of amorphous silica nanoparticles on Langerhans cells. Die Pharmazie 65 , — Liang, H. Cytotoxicity of silica nanoparticles on HaCaT cells.

Systemic distribution, nuclear entry and cytotoxicity of amorphous nanosilica following topical application. Ryu, H. Evaluation of silica nanoparticle toxicity after topical exposure for 90 days. Matsuo, K. Luckhaupt, S. Landis, E. Top dermatologic diagnoses by age. Dermatology online journal 20 , Helmick, C. Prevalence of psoriasis among adults in the U. Roberson, E. Psoriasis genetics: breaking the barrier.

De Benedetto, A. Tight junction defects in patients with atopic dermatitis. The Journal of allergy and clinical immunology , Wolf, R. Abnormal epidermal barrier in the pathogenesis of psoriasis. Lyons, J. Atopic dermatitis in children: clinical features, pathophysiology, and treatment. Jatana, S. Immunomodulatory Effects of Nanoparticles on Skin. Honda, T. Askenase, P.

THE DANGER MODEL: HOW THE IMMUNE SYSTEM CAN DISTINGUISH BETWEEN HARMFUL AND NON-HARMFUL ANTIGENS?

B-1 B cell IgM antibody initiates T cell elicitation of contact sensitivity. Current topics in microbiology and immunology , — A subset of AID-dependent B-1a cells initiates hypersensitivity and pneumococcal pneumonia resistance. Phanuphak, P. Tolerance and contact sensitivity to DNFB in mice. In vivo detection by ear swelling and correlation with in vitro cell stimulation.

Journal of immunology , — Welzel, J. Archives of dermatological research , — Krause, K. The role of interleukin-1 in allergy-related disorders. Dilulio, N. Groalpha-mediated recruitment of neutrophils is required for elicitation of contact hypersensitivity. European journal of immunology 29 , —, Biedermann, T. Kondo, S.

Watanabe, H.


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Girard-Madoux, M. IL controls dendritic cell-induced T-cell reactivation in the skin to limit contact hypersensitivity. Grone, A. Keratinocytes and cytokines. Veterinary immunology and immunopathology 88 , 1—12 Cassatella, M. Regulated production of the interferon-gamma-inducible protein IP chemokine by human neutrophils.

Drug-Induced Cutaneous Toxicity

Dufour, J. Krathwohl, M. Vocanson, M. Proksch, E. The skin: an indispensable barrier. Experimental dermatology 17 , — Larese Filon, F. Nanoparticles skin absorption: New aspects for a safety profile evaluation. Docter, D. The protein corona protects against size- and dose-dependent toxicity of amorphous silica nanoparticles. Engeman, T. The intensity of neutrophil infiltration controls the number of antigen-primed CD8 T cells recruited into cutaneous antigen challenge sites.

Wang, T. Enhanced mucosal and systemic immune responses obtained by porous silica nanoparticles used as an oral vaccine adjuvant: effect of silica architecture on immunological properties. Mody, K. Mesoporous silica nanoparticles as antigen carriers and adjuvants for vaccine delivery. Skrastina, D. Silica nanoparticles as the adjuvant for the immunisation of mice using hepatitis B core virus-like particles.

Enhancement of ovalbumin-specific Th1, Th2, and Th17 immune responses by amorphous silica nanoparticles. Hirai, T. Amorphous silica nanoparticles size-dependently aggravate atopic dermatitis-like skin lesions following an intradermal injection. Yanagisawa, R. Experimental biology and medicine Maywood, N. Smulders, S. Nano-TiO2 modulates the dermal sensitization potency of dinitrochlorobenzene after topical exposure. Cutaneous exposure to agglomerates of silica nanoparticles and allergen results in IgE-biased immune response and increased sensitivity to anaphylaxis in mice.

Ostrowski, A. AHAPS-functionalized silica nanoparticles do not modulate allergic contact dermatitis in mice. Bhol, K. Topical nanocrystalline silver cream suppresses inflammatory cytokines and induces apoptosis of inflammatory cells in a murine model of allergic contact dermatitis. Vemula, P. Nanoparticles reduce nickel allergy by capturing metal ions. Mortensen, L. The risk of occupational seafood-based protein contact dermatitis appears to be low in the populations that we studied. It is therefore difficult to draw statistical conclusions with so few occurrences.

The social security agency for professional seafarers has no recorded cases of protein contact dermatitis. These were always related to allergic contact dermatitis based on a delayed-type contact allergy rather than being related to protein contact dermatitis [ 12 — 14 ]. Moreover, having been described for the first time in , protein contact dermatitis is still a little-known disease and is hence probably under-diagnosed [ 1 , 15 ]. Additionally, our study is retrospective as it uses the registry for the compensation of occupational diseases.

The registry is non-exhaustive in its overview of skin diseases present in the fishing profession infectious, cancerous and other non-allergic skin diseases having been left out of the search. As such, the study selects only the patients who chose to have their skin problem diagnosed as well as to claim for compensation. In a fish preparation plant, Aasmoe et al. The study sheds light on the fact that, in a population of workers such as fishermen, who are accustomed to difficult working conditions, there is a relative trivialization of skin problems that are considered minor.

Such skin problems are therefore never mentioned to a health professional. Another explanation that needs to be considered is a healthy worker effect: affected workers may have left the industry of their own accord so as to prevent their health problem from worsening rather than gone to see a doctor about their dermatitis or gone as far as to declare the condition. Their positions are then filled exclusively by healthy individuals. This hypothesis is frequently put forward to explain the rarity of this pathology in occupations that are particularly at risk [ 16 , 17 ].

Type IV hypersensitivity (cell-mediated) - causes, symptoms, treatment & pathology

Nonetheless, we could also investigate the question of the positive protective influence of the maritime environment with regard to sensitivity to seafood proteins. Additionally, glove protection may limit exposure sufficiently to avoid triggering sensitivity. In this context, fishermen seem very diligent in wearing skin protection gear while carrying out their professional tasks, during which the risk of injury is also high [ 12 ].

Furthermore, atopy, which was frequent in the second population of professionals affected by protein contact dermatitis, is very infrequent in the seafaring population [ 13 ].

Contact dermatitis | American Academy of Dermatology

Certain atopic pathologies, such as unstable atopic asthma, make it difficult for sufferers to do these jobs, resulting in the exclusion of a population at risk of developing protein contact dermatitis. Among the other people working with seafood, the population of workers in seafood processing companies would logically be expected to be the most affected.

Among employees of seafood processing companies in France, however, no cases of protein contact dermatitis were recorded, in contrast with results in a number of publications [ 16 — 18 ]. When compared to major fish-producing countries such as Norway and South Africa, this result is surprising. As is the case for fishermen, the explanation may be that primary protection, such as wearing gloves and other protective clothing in factories may be sufficiently well applied so as to limit the occurrence of these diseases, in addition to a strict medical aptitude filter, which may exclude the more at-risk workers with atopic symptoms.

Given the employment statistics in France, fish processing jobs are often seasonal ones. Kalogermitros showed that the intensity and, more importantly, the duration of exposure are risk factors in fish processing companies, which perhaps explains the absence of cases among French workers since they frequently change jobs or careers [ 19 ]. Furthermore, the population of seasonal workers often bypasses occupational medical examinations, and thus workers under-report the occupational diseases that could subsequently be of harm to them.

The population of chefs is the most affected population in our study. They often handle fish bare-handed, which may explain the prevalence of protein contact dermatitis in our study. Moreover, there are other factors that influence the increased risk for protein contact dermatitis.

Halkier et al. In addition, the liquid from fish, which has a high protein content, has been recognised as a risk factor in several studies [ 16 , 21 ]. In a study by Aasmoe, those doing jobs involving filleting and bare-handed shrimp peeling were the most at risk among employees of a seafood processing plant [ 16 ].

Given the preparation techniques, it appears logical that chefs would be the most affected occupation. With salmon, there may be an added risk of protein contact dermatitis. The question of whether salmonid proteins are more sensitizing than proteins from other ocean fish warrants further investigation. Additionally, because the species can also be fished in fresh water and produced in aquaculture, it may be less often caught by fishermen at sea leading to a lower prevalence of associated skin problems in this population and a greater incidence in other groups.

Ultimately, the rarity of this dermatitis even among at-risk occupations can be explained, as is the case for fishermen, by the specificity of the files from occupational disease centres. Finally, this skin disease is perhaps under-diagnosed because of the recentness of its description and complex and unresolved aetiology. Many indeed believe that it may be triggered by a combination of type 1 and 4 reactions from the Gell and Coombs classification.

Arguments to support this are the existence of positive patch tests with more moderate reactions [ 23 ], the positive nature of scratch tests which allow for a better penetration of the allergen [ 24 ], the efficiency of corticoids as opposed to antihistamines, and the cutaneous symptoms with rare or minimal urticarial reactions [ 25 ].

Moreover, we were amazed by the absence in our population, as well as in the literature, of a description of systemic reactions during the ingestion of raw or cooked seafood by affected patients [ 7 ]. Only two cases were reported, and both were in patients with a filaggrin mutation, which is a known risk factor for allergic disease [ 26 , 27 ]. The physiopathology is therefore complex and needs to be clarified in order to gain a better understanding and make a better diagnosis of this pathology. Nevertheless in our study none of the patients with positive prick test results to seafood had corresponding specific IgE in the serum.

Chefs specifically those who work with seafood appear to be at higher risk of occupational protein contact dermatitis than fishermen. The influence of glove protection during fishing activities as compared to the bare-handed work of many chefs warrants further investigation. Furthermore, atopy that seems to be a risk factor among chefs is infrequent among fishermen. Indeed, the condition is frequently a reason for medical unfitness for onboard work, especially when the person has already suffered from unstable atopic asthma. Etablissement National des Invalides de la Marine the social security scheme for maritime professions.

Hjorth N, Roed-Petersen J. Occupational protein contact dermatitis in food handlers. Contact Dermatitis. Protein contact dermatitis: myth or reality? Br J Dermatol. Wuthrich B. Protein contact dermatitis. Garlic-related dermatoses: case report and review of the literature. Am J Contact Dermat. Doutre MS. Occupational contact urticaria and protein contact dermatitis. Eur J Dermatol. Expert Rev Clin Immunol. Amaro C, Goossens A. Immunological occupational contact urticaria and contact dermatitis from proteins: a review.

Springer-Verlag Berlin Heidelberg Edition; ISBN Therefore, it is more relevant to test the toxicity and potential immunomodulation of chronic, low dose exposures to SiNPs in models of inflammatory skin conditions. However, if used in a controlled manner, exposure to low doses of SiNPs could represent a safe and effective way to control symptoms of inflammatory skin conditions, like allergic contact dermatitis.

Although, these findings are preliminary, and additional research examining improved NP formulations and efficacy in human models would be required before therapeutic application of these NPs. Here we have characterized the downstream effects of 20 nm SiNPs in the CHS model, and identified keratinocytes as a potential upstream mediator of SiNP induced immunosuppression. However, the effect is not particle specific, since we observed that a number of small negatively charged NPs display CHS immunosuppression Due to the wide variety of sizes and surface chemistries of particles that reduce CHS symptoms, the mechanism of action is likely related to a general property of most NPs, like ROS generation 21 , For example, cigarette smoke exposure is known to suppress the ear swelling response in a model of CHS, and the mechanism involves the activation of platelet activating factor receptor by oxidized plasma membrane lipids There are relatively few studies examining the potential protective effects of SiNPs; however, research suggests that these NPs induce keratinocyte proliferation and expression of nuclear factor erythroid derived 2 -like 2 Nrf2 , a transcription factor for the antioxidant response element, after low dose exposure Another study found that Nrf2 induced follistatin production enhanced pulmonary epithelial cell survival, after exposure to SiNPs Since DNFB and other allergens induce high levels of oxidative stress in skin 33 , 77 , the SiNP induced expression of genes downstream of Nrf2 could have a protective effect on skin.

In fact, Nrf2 knockout mice were observed to have increased ear swelling responses after challenge with a chemical sensitizer Alternatively, a study also found that SiNPs induce autophagy as a pro-survival mechanism, after low dose exposure to a macrophage cell line In summary, while amorphous SiNPs are pro-inflammatory and cytotoxic at high doses, we have identified that topically applied, low doses of negatively charged 20 nm SiNPs are immunosuppressive in a DNFB induced model of allergic contact dermatitis.

The SiNPs decrease DNFB induced epidermal hyperplasia, skin cytokine expression, and cytotoxic T cell skin infiltration; which ultimately leads to less skin swelling. This immunomodulatory effect should be studied further, before SiNPs are used as transdermal drug delivery agents in patients with inflammatory skin conditions. The structure of the particles was analyzed by TEM, after spotting the undiluted NP mixtures onto copper grids. The mice were all males between the ages of 5—6 months, since we have observed age related differences in CHS response.

However, there is no observed difference in the CHS response between age matched male and female mice Supplementary Fig. After 24 hours, the mice were euthanized and the ear tissue was processed for histology, cytokine expression, and flow cytometric analysis. The HaCaT cells, an immortal keratinocyte cell line, was used in all in vitro assays. For the cytokine analysis, the cells were cultured in clear 96 well plates. For the cell death assay, the cells were cultured in white 96 well plates. The cells were treated with media containing either a 0. After 24 hours, the cell culture media was removed and frozen for future cytokine analysis.

After 15 minutes, the luminescence was measured with a Turner Biosystems Modulus microplate reader. The luminescence data relates to the amount of ATP in each well, which is directly related to the number of viable cells. The 0. A Nikon Eclipse E bright field microscope was used to image the skin histology slides, and epidermal thickness measures were obtained in 6 different images per sample, using ImageJ software All counts and measures were performed with a 20x microscope objective, and the counts or measures from 6—10 fields of view were averaged for each sample.

Analysis was only performed on the dorsal sides of the ear, due to the overt edema observed in the ventral sides of ears that made quantification difficult. The samples were mechanically homogenized and incubated on ice for 30 minutes. The samples were centrifuged for 5 minutes at 12, RPM to remove the skin debris. A BCA protein assay Pierce Cat was performed, and all cytokine measures were normalized to the total protein content in the ears.

After euthanasia, the mouse ears were removed, split in half, and processed into single cell suspensions; as previously reported Lastly, the samples were washed with PBS and then fixed with 2. Appropriate compensation controls and fluorescence minus one samples were used for calibrating the machine and gating the samples.

All flow cytometry data was converted to total cell counts per ear, using total cell counts obtained by manually counting the cells in each sample with a hemocytometer. Statistics were run using JMP Pro version A two-way analysis of variance with post-hoc Tukey tests were used for the histology, cytokine, flow cytometry, and cell culture data. Controlled growth of monodisperse silica spheres in the micron size range.

Contact dermatitis

Osseo-Asare, K. Preparation of SiO 2 nanoparticles in a non-ionic reverse micellar system. Sulpizi, M. Auffan, M. Towards a definition of inorganic nanoparticles from an environmental, health and safety perspective. Contado, C. Nanomaterials in consumer products: a challenging analytical problem.

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Sapino, S. Mesoporous silica as topical nanocarriers for quercetin: characterization and in vitro studies. European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e. Mesoporous silica nanoparticles as a promising skin delivery system for methotrexate. Nafisi, S. International journal of pharmaceutics. Robinson, K. Demento, S. Inflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy.

Wibowo, N. Co-administration of non-carrier nanoparticles boosts antigen immune response without requiring protein conjugation. Navarro-Tovar, G. An overview on the role of silica-based materials in vaccine development. Scheiblhofer, S. Potential of nanoparticles for allergen-specific immunotherapy - use of silica nanoparticles as vaccination platform.

Brandenberger, C.

Publication details

Engineered silica nanoparticles act as adjuvants to enhance allergic airway disease in mice. Han, H. Toxic and adjuvant effects of silica nanoparticles on ovalbumin-induced allergic airway inflammation in mice. Morris, A. Amine modification of nonporous silica nanoparticles reduces inflammatory response following intratracheal instillation in murine lungs. Parveen, A. Intranasal exposure to silica nanoparticles induces alterations in pro-inflammatory environment of rat brain. Hassankhani, R. In vivo toxicity of orally administrated silicon dioxide nanoparticles in healthy adult mice.

Toda, T. Amorphous nanosilica particles block induction of oral tolerance in mice. Nabeshi, H. Size-dependent cytotoxic effects of amorphous silica nanoparticles on Langerhans cells. Die Pharmazie 65 , — Liang, H. Cytotoxicity of silica nanoparticles on HaCaT cells. Systemic distribution, nuclear entry and cytotoxicity of amorphous nanosilica following topical application. Ryu, H. Evaluation of silica nanoparticle toxicity after topical exposure for 90 days. Matsuo, K. Luckhaupt, S.

Landis, E. Top dermatologic diagnoses by age. Dermatology online journal 20 , Helmick, C. Prevalence of psoriasis among adults in the U. Roberson, E. Psoriasis genetics: breaking the barrier. De Benedetto, A. Tight junction defects in patients with atopic dermatitis. The Journal of allergy and clinical immunology , Wolf, R. Abnormal epidermal barrier in the pathogenesis of psoriasis. Lyons, J. Atopic dermatitis in children: clinical features, pathophysiology, and treatment.


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Jatana, S. Immunomodulatory Effects of Nanoparticles on Skin. Honda, T.

Toxicology of Contact Hypersensitivity Toxicology of Contact Hypersensitivity
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Toxicology of Contact Hypersensitivity Toxicology of Contact Hypersensitivity
Toxicology of Contact Hypersensitivity Toxicology of Contact Hypersensitivity
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