The Distribution of 2,4-Dinitrophenyl Groups in Guinea Pig Skin Following Surface Application of 2,4-Dinitrochlorobenzene: An Immunofluorescent Study

Nakagawa, Shojiro; Ueki, Hiroaki; Tanioku, K

doi:10.1111/1523-1747.ep12261593

Cited by 27 publications

(23 citation statements)

References 12 publications

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“…Dinitrochlo robenzene (DNCB) penetrates the epidermis very rapidly: specific fluorescence was observed throughout the epider mis 1 min after epicutaneous painting with DNCB in the guinea pig [1]. Most of the DNCB is absorbed through the skin via the venous and lymphatic systems.…”

Section: Introductionmentioning

confidence: 99%

“…Human studies reveal broadly similar findings, with DNCB localized in the upper epidermis at 1 h after chal lenge and detectable on sweat duct and hair follicle epithelia at 3 h [3], Studies using radioactive nickel applied to the skin surface showed 65% absorption within 24 h. there being no difference between nickel-sensitive and non-nickel-sensitive subjects [4], DNCB has been demonstrated on epidermal cell membranes at 3 h in epidermal sheets from guinea pigs [5], Cytoplasmic localization has also been demonstrated in epidermal cells [1], including both keratinocytes and Langerhans cells [6. 7], DNCB-reactive cells are noted in the upper dermis as early as 6 min in animal studies [1] and at 6 h in humans [3].…”

Section: Introductionmentioning

confidence: 99%

“…7], DNCB-reactive cells are noted in the upper dermis as early as 6 min in animal studies [1] and at 6 h in humans [3]. In experimental models using animals sensitized to DNCB or dinitrofluorobenzene (DNFB).…”

Section: Introductionmentioning

confidence: 99%

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The Hapten in Contact Hypersensitivity to Dinitrochlorobenzene: Immunoelectron Microscopic and Immunofluorescent Studies

Gawkrodger

Haftek

Botham³

et al. 1989

Dermatology

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Six hours after challenge with dinitrochlorobenzene (DNCB) in sensitized volunteers, infrequent cells reacting with both OKT6 (CD 1a) and with an antibody to DNCB were demonstrated in the upper dermis in 3 out of 4 subjects, using a double fluorescence technique. Single marker studies using polyclonal and monoclonal antibodies to DNCB showed cytoplasmic reactivity with peripheral accentuation in keratinocytes throughout the epidermis, most intense in the granular and basal layers, and occasional positive cells in the papillary dermis. Immunoperoxidase electron microscopy using polyclonal and monoclonal antibodies to DNCB demonstrated reactivity on keratinocyte and Langerhans cell membranes, with intracellular deposition of reaction product on mitochondria. Reaction product was present on the external leaflets of Birbeck granules, suggesting that the penetration of DNCB was passive rather than due to an active endocytic process. The immunofluorescent studies suggest that the double-fluorescing upper dermal cells were Langerhans cells but this could not be confirmed by electron microscopy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Hapten in Contact Hypersensitivity to Dinitrochlorobenzene: Immunoelectron Microscopic and Immunofluorescent Studies

Gawkrodger

Haftek

Botham³

et al. 1989

Dermatology

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“…Our previous investigation [7], in which localization of 2,4-dinitrophenyl (DNP) groups in the skin of guinea pigs following painting with 2,4-dinitrochlorobenzene (DNCB) was examined by the immunofluo rescent method using anti-DNP antibody, showed that DNP groups were distributed on/in epidermal cells. The cells in which DNP groups were detectable (DNP cells) were shown to account for approximately 90% of the epidermal cells [9], This indicates that the majority of DNP cells are kératino cytes.…”

Section: Introductionmentioning

confidence: 99%

Distribution of 2,4-Dinitrophenyl Groups on the Epidermal Langerhans Cells of Guinea Pigs following Skin Painting with 2,4-Dinitrochlorobenzene

Oka¹,

Nakagawa²,

Oota³

et al. 1986

Dermatology

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It has been postulated that epidermal Langerhans cells (LC) are essential for induction and elicitation of contact sensitivity (CS) to simple chemical allergens. Although the precise role of LC in CS has not been determined, recent reports have focused on a function for LC in the presentation of antigen to T lymphocytes. To investigate this possibility, the distribution of allergen on the epidermal LC of inbred strain 13 guinea pigs was observed by the immunofluorescent method using antibodies against la antigen and hapten. 2,4-Dinitrophenyl groups were found to be localized on/in Ia-positive epidermal LC of the animals following skin painting with 2,4-dinitrochlorobenzene. This finding is discussed in relation to the role of LC as antigen presenting cells in CS.

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“…This reaction results in the formation of dinitrophenylated proteins which are recognized as foreign by the immune system (20). It has been shown previously that DNCB readily penetrates the skin of humans and monkeys (3)and that followingapplication ofDNCB, dinitrophenylated proteins can be detected in draining lymph nodes (19). Because DNCB reacts with structural as well as soluble proteins, it acts as a persistent antigen which favors formation of cellular as opposed to humoral immunity.…”

Section: Discussionmentioning

confidence: 99%

Effects of Sensitization to Dinitrochlorobenzene (DNCB) on Clinical Pathology Parameters and Mitogen-Mediated Blastogenesis in Cynomolgus Monkeys (Macaca, fascicularis)

et al. 1990

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Immunotoxicologic testing of drug candidates and environmental contaminants is of growing importance. Cutaneous delayed type hypersensitivity (OTH) is a convenient way of testing immune function in vivo.However, OTH testing must not interfere with interpretation of other relevant parameters. We have evaluated the effects of sensitization and challenge with dinitrochlorobenzene (ONCB) on clinical parameters routinely evaluated in toxicity testing and on lectin-mediated blastogenesis. Female cynomolgus monkeys were sensitized to ONCB with 4 daily applications of ONCB in acetone to the skin of the axilla. Fifteen days later, the monkeys were challenged for OTH by applying ONCB to the antecubital skin. Skin fold thickness was measured and the macroscopic appearance of the challenge site was scored 24 and 48 hr after challenge. All 5 monkeys were successfully sensitized to ONCB. There was a significant increase in the mean skin fold thickness (compared to pre-challenge thickness) of 2 mm at 24 hr and 1 mm at 48 hr (p < 0.001). The clinical score of the challenge site was also increased. Histologic examination of the sensitization and challenge sites from a second group of monkeys exposed to ONCB in an identical manner showed the perivascular inflammatory cell infiltrate typical of OTH. Evaluation of hematologic parameters at days 7, 14, and 21 revealed no change in the erythron at any interval and a mild decrease in total WBC, neutrophil and lymphocyte counts on day 7 in 4/5 monkeys. The WBC parameters remained within the normal range and returned to pre-sensitization values at the later intervals. Clinical biochemical parameters related to liver and kidney function were evaluated at the same intervals and no changes were found. The blastogenic response of peripheral blood leukocytes to concanavalin A, phytohemagglutinin and pokeweed mitogen was mildly but not significantly decreased at day 7 but not on day 14 or 21. This study has shown that sensitization to ONCB in cynomolgus monkeys is a reliable means of evoking a OTH response which is quantifiable. It has also shown that sensitization and challenge with ONCB can be incorporated into toxicity studies without confounding interpretation of other toxicity data.

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The Distribution of 2,4-Dinitrophenyl Groups in Guinea Pig Skin Following Surface Application of 2,4-Dinitrochlorobenzene: An Immunofluorescent Study

Cited by 27 publications

References 12 publications

The Hapten in Contact Hypersensitivity to Dinitrochlorobenzene: Immunoelectron Microscopic and Immunofluorescent Studies

The Hapten in Contact Hypersensitivity to Dinitrochlorobenzene: Immunoelectron Microscopic and Immunofluorescent Studies

Distribution of 2,4-Dinitrophenyl Groups on the Epidermal Langerhans Cells of Guinea Pigs following Skin Painting with 2,4-Dinitrochlorobenzene

Effects of Sensitization to Dinitrochlorobenzene (DNCB) on Clinical Pathology Parameters and Mitogen-Mediated Blastogenesis in Cynomolgus Monkeys (Macaca, fascicularis)

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