The Vehicle Modulates Cellular and Humoral Responses in Contact Hypersensitivity to Oxazolone

Erve, E. H. M. van't; Wijnand, E.; Bol, M.; Seinen, Willem; Pieters, Raymond

doi:10.1093/toxsci/44.1.39

Cited by 13 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It must be emphasized that the vehicle in which a chemical is Copyright applied to the skin can have a very significant impact on the vigour of lymph node cell (LNC) proliferative responses and the efficiency with which sensitization is acquired. [26][27][28][29] This point will be considered again later in this article. Five days following the initiation of exposure, all mice receive an intravenous injection of 3 H-labelled thymidine ([ 3 H]TdR).…”

Section: Conduct Of the Local Lymph Node Assaymentioning

confidence: 94%

“…As indicated previously in this article, there is strong evidence that the matrix in which a chemical allergen is encountered on the skin can have a substantial, or even profound, effect on the acquisition of contact sensitization. [26][27][28][29] It is possible that one way in which the vehicle might affect the efficiency of sensitization is through alterations in skin penetration and bioavailability of the chemical allergen. However, other factors may be important and the ability of application vehicles to modify metabolic processes in the skin (such as to influence the conversion of prohaptens to haptens or to modify detoxification processes) cannot be discounted.…”

Section: Potency and Risk Assessmentmentioning

confidence: 99%

See 1 more Smart Citation

Local lymph node assay: use in hazard and risk assessment

1999

View full text Add to dashboard Cite

The murine local lymph node assay (LLNA) was developed as an alternative method for the identification of chemicals that have the ability to cause skin sensitization and allergic contact dermatitis. The assay now has been evaluated extensively in the context of both national and international inter‐laboratory collaborative trials and has been the subject of detailed comparisons with guinea pig test methods and human skin sensitization data. On the basis of these evaluations the LLNA has been endorsed recently by the US Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) as a stand‐alone method for skin sensitization testing. The assay offers a number of important benefits compared with conventional guinea pig test methods, among these being provision of an objective and quantitative endpoint. Moreover, the LLNA provides advantages in the context of animal welfare; compared with guinea pig tests, fewer animals are required and these animals are subject to less trauma. It is important now that the validation status of the LLNA is recognized and the method applied widely so that these advantages may be realized. Hazard identification represents only the first step in the risk assessment process. A full toxicological evaluation of skin sensitization activity requires an understanding of relative potency. Guinea pig methods do not lend themselves readily to assessment of potency, and interest recently has focused on the utility of the LLNA for this purpose. Contained within this review article are brief descriptions of the history of the LLNA and the immunobiological basis for the method, together with detailed accounts of the conduct and interpretation of the assay. Procedural modifications to, and alternative endpoints for, the LLNA are considered also. Finally, the current regulatory status of the LLNA is summarized and the application of the method for the purposes of defining relative potency and developing risk assessments is reviewed. Copyright © 1999 John Wiley & Sons, Ltd.

show abstract

Section: Conduct Of the Local Lymph Node Assaymentioning

confidence: 94%

Section: Potency and Risk Assessmentmentioning

confidence: 99%

Local lymph node assay: use in hazard and risk assessment

1999

View full text Add to dashboard Cite

show abstract

“…This suggests that DMSO may in itself have an immunosuppressive effect at this level. Previously, van't Erve et al (1998) showed that treatment with DMSO led to a reduction in IgG production in mice. Similarly, Pestronk and Drachman (1980) showed that DMSO significantly reduced antibody production in rats.…”

Section: Discussionmentioning

confidence: 99%

Short-term exposure of Chinook salmon (Oncoryhnchus tshawytscha) to o,p-DDE or DMSO during early life-history stages causes long-term humoral immunosuppression.

Milston

Fitzpatrick

Vella

et al. 2003

Environ Health Perspect

View full text Add to dashboard Cite

We evaluated the effect of short-term exposures to a xenobiotic chemical during early life-history stages on the long-term immune competence of chinook salmon (Oncoryhnchus tshawytscha). Immersion of chinook salmon eggs in a nominal concentration of o,p´-dichlorodiphenyldichloroethylene (o,p´-DDE; 10 ppm) for 1 hr at fertilization followed by immersion in the same dose for 2 hr at hatch resulted in a significant reduction in the ability of splenic leukocytes from fish 1 year after treatment to undergo blastogenesis upon in vitro stimulation with lipopolysaccharide. We also observed that the vehicle, dimethyl sulfoxide (DMSO), caused a significant reduction in the ability of the splenic leukocytes to express surface immunoglobin M (SIgM) at this time. The concentration of o,p´-DDE in a pooled sample of whole fry from this treatment was 0.53 µg/g lipid 1 month after first feeding but was undetectable in all other treatments. Mortality rate, time to hatch, fish length, and weight were unaffected by treatment with o,p´-DDE. Similarly, sex ratios, gonadal development, and concentrations of plasma estradiol and 11-ketotestosterone were not affected by the treatment. In addition, we found no evidence that plasma lysozyme concentrations or the mitogenic responses of splenic leukocytes to concanavalin A or polyinosinic-polycytidylic acid were influenced by the treatment. In this experiment, a brief period of exposure to o,p´-DDE or DMSO during early development was able to induce long-term effects on humoral immune competence of chinook salmon. Such immunosuppression may increase susceptibility to disease, which may in turn be critical to regulating the population.

show abstract

“…Consistent with the early reports of haemagglutinating antibodies , skin sensitization with oxazolone also induces a hapten‐specific IgG response in mice, as measured by ELISA . In those murine studies where the isotype of the IgG response has been characterized, detectable anti‐hapten IgG1, IgG2a and IgG2b production has been recorded , with several reports of a preferential IgG2a response to both DNCB and oxazolone , consistent with selective Th1 cell activation. Interestingly, there are also reports that IgE may also be detected following topical exposure of mice to contact allergens, particularly when there is repeated skin exposure and through abraded or damaged skin .…”

Section: Anti‐hapten Antibody Responses Induced Following Exposure Tomentioning

confidence: 99%

Anti‐hapten antibodies in response to skin sensitization

et al. 2015

View full text Add to dashboard Cite

SummaryWhereas T lymphocyte (T cell) activation is the key event in the acquisition of skin sensitization and subsequent elicitation of allergic contact dermatitis, the humoral component of immune responses to organic contact allergens has received little consideration. There is evidence that, in experimental animals, topical exposure to potent contact allergens is associated with B cell activation and proliferation, and hapten-specific antibody production. However, there is very limited evidence available for anti-hapten antibody responses being induced following topical exposure of humans to contact allergens. Nevertheless, it is important to appreciate that there are almost no negative studies in which evidence for antibody production as the result of skin sensitization has been sought and not found. That is, there is absence of evidence rather than evidence of absence. Furthermore, exposure to chemical respiratory allergens, in which the skin has been implicated as a potential route of sensitization, results in anti-hapten antibody responses. It is proposed that skin sensitization to contact allergens will normally be accompanied by antibody production. The phenomenon is worthy of investigation, as anti-hapten antibodies could potentially influence and/or regulate the induction of skin sensitization. Moreover, such antibodies may provide an informative correlate of the extent to which sensitization has been acquired.Key words: allergic contact dermatitis; antibody response; B cell; hapten; IgG; IgM; skin sensitization.From an immunological perspective, the acquisition of skin sensitization and the elicitation of allergic contact dermatitis are immune and inflammatory responses mediated by antigen (hapten)-specific T cells (1-3). For this reason, it is the activation, differentiation and regulation of T cells upon which attention has been focused, and there are available excellent recent reviews that describe Accepted for publication 21 September 2015the roles played by T cells in skin sensitization and allergic contact dermatitis (4-7).However, at least in animals, contact allergens provoke both humoral and cell-mediated immune responses. Thus, topical encounter with a contact allergen will induce anti-hapten antibody formation in addition to the activation and expansion of responsive T cells (8-10). Given the predominant role played by T cells in skin sensitization, it is perhaps not surprising that anti-hapten antibody responses have received comparatively little attention. This is unfortunate because, in theory, a hapten-specific antibody has the ability to influence both the acquisition of skin sensitization and the subsequent elicitation of allergic reactions. Moreover, it is possible that the vigour and isotype distribution of anti-hapten antibodies induced by exposure to contact allergens

show abstract

The Vehicle Modulates Cellular and Humoral Responses in Contact Hypersensitivity to Oxazolone

Cited by 13 publications

References 0 publications

Local lymph node assay: use in hazard and risk assessment

Local lymph node assay: use in hazard and risk assessment

Short-term exposure of Chinook salmon (Oncoryhnchus tshawytscha) to o,p-DDE or DMSO during early life-history stages causes long-term humoral immunosuppression.

Anti‐hapten antibodies in response to skin sensitization

Contact Info

Product

Resources

About