RESUMEN
Zinc deficiency can be an inherited disorder, in which case it is known as acrodermatitis enteropathica (AE), or an acquired disorder caused by low dietary intake of zinc. Even though zinc deficiency diminishes cellular and humoral immunity, patients develop immunostimulating skin inflammation. Here, we have demonstrated that despite diminished allergic contact dermatitis in mice fed a zinc-deficient (ZD) diet, irritant contact dermatitis (ICD) in these mice was more severe and prolonged than that in controls. Further, histological examination of ICD lesions in ZD mice revealed subcorneal vacuolization and epidermal pallor, histological features of AE. Consistent with the fact that ATP release from chemically injured keratinocytes serves as a causative mediator of ICD, we found that the severe ICD response in ZD mice was attenuated by local injection of soluble nucleoside triphosphate diphosphohydrolase. In addition, skin tissue from ZD mice with ICD showed increased levels of ATP, as did cultured wild-type keratinocytes treated with chemical irritants and the zinc-chelating reagent TPEN. Interestingly, numbers of epidermal Langerhans cells (LCs), which play a protective role against ATP-mediated inflammatory signals, were decreased in ZD mice as well as samples from ZD patients. These findings suggest that upon exposure to irritants, aberrant ATP release from keratinocytes and impaired LC-dependent hydrolysis of nucleotides may be important in the pathogenesis of AE.
Asunto(s)
Acrodermatitis/patología , Acrodermatitis/fisiopatología , Dermatitis Alérgica por Contacto/patología , Dermatitis Alérgica por Contacto/fisiopatología , Células de Langerhans/inmunología , Piel/citología , Zinc/deficiencia , Acrodermatitis/dietoterapia , Adenosina Trifosfato/metabolismo , Animales , Células Cultivadas , Quimiocinas/genética , Quimiocinas/metabolismo , Dermatitis Alérgica por Contacto/dietoterapia , Suplementos Dietéticos , Femenino , Humanos , Queratinocitos/citología , Queratinocitos/metabolismo , Queratinocitos/patología , Células de Langerhans/citología , Ratones , Ratones Endogámicos BALB C , Piel/metabolismo , Piel/patología , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
OBJECTIVE: To investigate the possible mechanism of local hyperthermia in the treatment of warts through detecting the differences in CD1a/CD83 of Langerhans cells (LCs) in émigrés from HPV-infected skin, as compared to normal skin. METHODS: Confocal microscopy were performed on Condyloma Accuminatum (CA)and normal skin; Freshly taken biopsies of CA and normal skin were subjected to surface heating at 37 degrees C, 42 degrees C and 45 degrees C respectively, for 30 mins. Flow cytometry was used to determine the CD1a/ CD83 changes of LCs in émigrés from CA and normal skin. RESULTS: By confocal microscopic observation, there were practically no CD1a+ LCs that expressed CD83 in the epidermis of both normal skin and CA. The proportions of CD1a+/CD83 LCs were significantly increased with increased temperatures in émigrés from both normal skin and CA. At each given temperature, the numbers of LCs in émigrés from CA were greater than those from normal skin. CONCLUSION: Local hyperthermia can promote migration and maturation of LCs in HPV-infected skin and accordingly stimulate the immune system to treat warts.
Asunto(s)
Hipertermia Inducida , Células de Langerhans/citología , Papillomaviridae/inmunología , Piel/inmunología , Piel/virología , Adulto , Movimiento Celular/inmunología , Femenino , Humanos , Técnicas In Vitro , Células de Langerhans/inmunología , Papillomaviridae/patogenicidad , Adulto JovenRESUMEN
In this report, we have addressed the effect of oral administration of a hydrophilic extract of the fern Polypodium leucotomos (PL) on the deleterious effects of ultraviolet radiation (UVR) on the levels of epidermal and plasmatic antioxidants in hairless rats. We have found that pretreatment with PL effectively reduced glutathione oxidation in both blood and epidermis, suggesting a potent systemic antioxidant effect. In addition, PL inhibited UVR-mediated Langerhans cell (LC) depletion. Our results demonstrate the efficacy of PL as an oral antioxidant and photoimmunoprotective agent and support its employment as a complement to topical sunscreens.
Asunto(s)
Glutatión/metabolismo , Células de Langerhans/efectos de los fármacos , Células de Langerhans/efectos de la radiación , Polypodium , Rayos Ultravioleta/efectos adversos , Administración Oral , Animales , Antioxidantes/administración & dosificación , Antioxidantes/metabolismo , Catalasa/metabolismo , Recuento de Células , Células Epidérmicas , Epidermis/efectos de los fármacos , Epidermis/efectos de la radiación , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Eritrocitos/efectos de la radiación , Glutatión/sangre , Disulfuro de Glutatión/sangre , Disulfuro de Glutatión/metabolismo , Células de Langerhans/citología , Células de Langerhans/inmunología , Masculino , Oxidación-Reducción , Extractos Vegetales/administración & dosificación , Protectores contra Radiación/administración & dosificación , Ratas , Ratas sin PeloRESUMEN
Triptolide (TPT) is a chemically defined, potent immunosuppressive compound isolated from an anti-inflammatory Chinese herbal medicine. TPT has been reported to inhibit autoimmunity, allograft rejection, and graft-versus-host disease (GVHD), and its efficacy was previously attributed to the suppression of T cells. Since dendritic cells (DCs) play a major role in the initiation of T-cell-mediated immunity, we studied the effects of TPT on the phenotype, function, and migration of human monocyte-derived DCs. TPT treatment, over a pharmacologic concentration range, inhibited the lipopolysaccharide (LPS)-induced phenotypic changes, characteristic of mature DCs and the production of interleukin-12p70 (IL-12p70). Consequently, the allostimulatory functions of DCs were impaired by TPT treatment. Furthermore, the calcium mobilization and chemotactic responses of LPS-stimulated DCs to secondary lymphoid tissue chemokine (SLC)/CC chemokine ligand 21 (CCL21) were significantly lower in TPT-treated than untreated DCs, in association with lower chemokine receptor 7 (CCR7) and higher CCR5 expression. Egress of Langerhans cells (LCs) from explanted mouse skin in response to macrophage inflammatory protein-3beta (MIP-3beta)/CCL19 was arrested by TPT. In vivo administration of TPT markedly inhibited hapten (fluorescein isothiocyanate [FITC])-stimulated migration of mouse skin LCs to the draining lymph nodes. These data provide new insight into the mechanism of action of TPT and indicate that the inhibition of maturation and trafficking of DCs by TPT contributes to its immunosuppressive effects.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Células Dendríticas/citología , Diterpenos/química , Diterpenos/farmacología , Medicamentos Herbarios Chinos/farmacología , Inmunosupresores/farmacología , Fenantrenos/química , Fenantrenos/farmacología , Animales , Apoptosis , Autoinmunidad , Complejo CD3/biosíntesis , Linfocitos T CD4-Positivos/citología , Calcio/metabolismo , Diferenciación Celular , Movimiento Celular , Separación Celular , Quimiocina CCL19 , Quimiocina CCL21 , Quimiocinas CC/metabolismo , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Epidermis/metabolismo , Compuestos Epoxi , Femenino , Citometría de Flujo , Fluoresceína-5-Isotiocianato/farmacología , Interleucina-12/metabolismo , Células de Langerhans/citología , Leucocitos Mononucleares/citología , Lipopolisacáridos/metabolismo , Ganglios Linfáticos/patología , Ratones , Ratones Endogámicos BALB C , Monocitos/citología , Monocitos/metabolismo , Fenotipo , Subunidades de Proteína/metabolismo , Receptores CCR5/metabolismo , Piel/metabolismoRESUMEN
BACKGROUND: Migration and maturation of epidermal dendritic cells, the Langerhans cells (LC), are central events in the initiation of the cutaneous immune response. LC migration from skin to draining lymph nodes is regarded as an indispensable step for the early phase of antigen-specific sensitization. Among the several agents which influence the ability of LC to migrate, previous studies have revealed that matrix metalloproteinases (MMPs) and protein kinase C (PKC) contribute to promoting LC migration. In this work, we studied the effect of two recently developed PKC and MMPs inhibitors of vegetable origin on the migration of in vitro activated LC. METHODS: The migratory capacity of epidermal and in vitro generated LC was assessed using a reconstituted basement membrane assay (Matrigel), mimicking the prerequisite passage through the dermal-epidermal basement membrane on the way to the lymph nodes. RESULTS: Contact with chemical allergens, Bandrowski's base or 2,4-dinitrobenzenesulfonic acid (DNBS), triggered migration. In the presence of PKC inhibitors, D-erythro-sphingosine and OX100, or an inhibitor of MMPs, LU105, allergen-induced migration of LC was strongly decreased. The association between OX100 and LU105 was more efficient in modulating the migration of activated LC compared to each molecule tested separately. CONCLUSIONS: These results showed that PKC and MMPs inhibitors act in synergy to inhibit the migration of activated epidermal dendritic cells in vitro. They underscore the role of PKC and MMPs inhibitors and suggest they may be of relevance for therapeutically regulating epidermal dendritic cell migration in inflammatory dermatoses.
Asunto(s)
Dermatitis por Contacto/inmunología , Inhibidores Enzimáticos/farmacología , Células de Langerhans/efectos de los fármacos , Células de Langerhans/inmunología , Inhibidores de la Metaloproteinasa de la Matriz , Proteína Quinasa C/antagonistas & inhibidores , Esfingosina/farmacología , Antígenos CD/inmunología , Antígenos CD1/inmunología , Antígeno B7-2 , Bencenosulfonatos/inmunología , Inhibición de Migración Celular , Dermatitis por Contacto/tratamiento farmacológico , Sinergismo Farmacológico , Citometría de Flujo , Humanos , Células de Langerhans/citología , Células de Langerhans/enzimología , Lupinus , Metaloproteinasas de la Matriz/inmunología , Glicoproteínas de Membrana/inmunología , Oligopéptidos/farmacología , Oxazoles/farmacología , Fenilendiaminas/inmunología , Extractos Vegetales/farmacología , Proteína Quinasa C/inmunologíaRESUMEN
Selenium (Se) is a dietary trace element that is essential for effective immunity and protection from oxidative damage induced by ultraviolet radiation (UVR). Langerhans cells (LC) represent the major antigen-presenting cells resident in the epidermis; a proportion migrate from the skin to the draining lymph nodes in response to UVR. Because it is known that Se deficiency impairs immune function, we determined what effect this has on LC numbers. CH3/HeN mice were weaned at 3 wk and placed on diets containing <0.005 ppm of Se (Se deficient) or 0.1 ppm of Se (Se adequate, control mice). After 5 wk on the diet, the epidermal LC numbers in the Se-adequate group were 966 +/- 51 cells/mm2 and LC counts in the epidermis of the Se-deficient mice were 49% lower (p<0.05). Glutathione peroxidase- I (GPx) activity was measured in the epidermis, lymph nodes, and liver. In the epidermis, the activity of GPx in the Se-deficient mice was only 39% (p<0.01) of that seen in epidermis from Se-adequate mice (1.732 U/mg protein). The mice were then irradiated with one dose of 1440 J/m2 of broadband UVB or mock irradiated. After 24 h, the decrease in LC number after UVB was greater in the Se-adequate mice, (40% decrease) compared to the Se-deficient group (10%). Thus, Se deficiency reduces epidermal LC numbers, an effect that might compromise cutaneous immunity.
Asunto(s)
Células Epidérmicas , Células de Langerhans/citología , Selenio/deficiencia , Selenio/farmacología , Rayos Ultravioleta , Adenosina Trifosfatasas/análisis , Adenosina Trifosfatasas/efectos de la radiación , Animales , Recuento de Células , Dieta , Epidermis/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Células de Langerhans/efectos de los fármacos , Células de Langerhans/efectos de la radiación , Ratones , Selenio/administración & dosificación , Factores de Tiempo , Aumento de Peso/efectos de los fármacosRESUMEN
Langerhans cells are the most potent antigen-presenting cells in the skin and play a critical role in the induction of contact allergy. Research on the phenotypical and functional changes of LCs occurring after application of skin sensitizers indicated their use as an in vitro model for the screening of chemicals. In the present investigations, LCs from human skin explants served as the test system. The application of this cell system has been aggravated by the difficulty in isolating sufficient numbers of live LCs from skin. This disadvantage was overcome by the culture of immature dendritic cells from peripheral mononuclear blood cells. These cells can serve as a replacement for LCs as they bind haptens and show phenotypical and functional changes similar to LCs. The sensitizers NiSO(4), dinitrochlorobenzene, 2,4,6-trinitrobenzene sulfonic acid, alpha-hexylcinnamaldehyde and eugenol were applied. Both the expression of surface markers and the induction of intracellular interleukin-1 beta (IL-1 beta) were analyzed. No clear-cut results could be established for intracellular cytokine production, only NiSO(4) induced a remarkable number of IL-1 beta-positive cells. However, all skin sensitizers caused an up-regulation of the co-stimulatory molecule CD86, of intercellular adhesion molecule CD54 and of the HLA-DR antigen. The irritant sodium dodecyl sulfate (SDS) and the vehicle dimethyl sulfoxide (DMSO) had no effect.
Asunto(s)
Acroleína/análogos & derivados , Alérgenos/toxicidad , Células Dendríticas/efectos de los fármacos , Evaluación Preclínica de Medicamentos/métodos , Células de Langerhans/efectos de los fármacos , Acroleína/toxicidad , Alternativas a las Pruebas en Animales , Antígenos CD/metabolismo , Antígenos de Superficie/biosíntesis , Antígeno B7-2 , Células Cultivadas , Células Dendríticas/citología , Células Dendríticas/metabolismo , Dinitroclorobenceno/toxicidad , Eugenol/toxicidad , Citometría de Flujo , Humanos , Interleucina-1/biosíntesis , Células de Langerhans/citología , Células de Langerhans/metabolismo , Glicoproteínas de Membrana/metabolismo , Modelos Biológicos , Monocitos/citología , Níquel/toxicidad , Piel , Ácido Trinitrobencenosulfónico/toxicidad , Regulación hacia ArribaRESUMEN
BACKGROUND: The safety and efficacy of sublingual immunotherapy have been demonstrated in moderate allergic asthma and seasonal rhinitis. However, not much is known about the precise mechanism of action of the allergen when it crosses the oral mucosa. OBJECTIVE: To define this mechanism, we investigated the role of Langerhans' cells in the capture and internalization of allergens. METHODS: We generated dendritic cells in vitro with the phenotypic characteristics of Langerhans-like dendritic cells (LLDCs) from cord blood CD34(+) progenitors. We used two recombinant major allergens: Bet v 1 and Phl p 1 labeled with FITC. RESULTS: Internalization of allergens and control proteins was dose- and time-dependent and related to the immature state of the cells. LLDCs internalized allergens with a high efficiency in comparison with control molecules. Allergens were only internalized by macropinocytosis, as demonstrated by the use of various inhibitors. Addition of intracellular pH-modifying molecules indicated that only a part of the allergens was accumulated in acidic vesicles, whereas the majority remained in other cytoplasmic structures. Pulse-chase experiments calculated a half-life of 4 hours, suggesting that part of the molecules were not metabolized in the lysosome. Allergen internalization by LLDCs might be followed by processing in some experiments, as demonstrated by activation of autologous T lymphocytes in 4 of 9 experiments. CONCLUSION: These elements showed that Langerhans' cells present in mucosa might play an active role in immune responses to allergens.
Asunto(s)
Alérgenos/inmunología , Sangre Fetal/citología , Células de Langerhans/citología , Polen/inmunología , Linfocitos T/inmunología , Separación Celular , Humanos , Activación de Linfocitos/inmunología , Pinocitosis/inmunología , Proteínas Recombinantes/inmunología , Células Madre/citologíaRESUMEN
Langerhans cells are bone marrow derived dendritic cells that represent the major antigen-presenting cells in the skin. Langerhans cells take up and process antigen within the epidermis and present processed antigen to T lymphocyte in the regional lymph nodes and thus form an integral part of the cutaneous immune response. The cutaneous immune response can be modified by a number of pharmacologic agents, including corticosteroids, cyclosporine, and retinoids as well as physical agents, such as ultraviolet light. For the most part these agents act by suppressing immune function. A topical immune response modifier, imiquimod has been shown to enhance the cutaneous immune response. Imiquimod has anti-viral and anti-tumor effects in animal models and has been approved for the topical treatment of external genital and perianal warts in humans. The biologic activity of imiquimod in part is due to its effect as a cytokine inducer. Preliminary data suggested that imiquimod could have an effect on Langerhans cells. In order to clarify this effect on Langerhans cells, we examined Langerhans cell morphology and migration in imiquimod-treated skin. The density of Ia + cells decreased 2 d after treatment, falling to approximately 43% by day 10. The Ia positive in cells remaining in the skin appeared larger and more dendritic suggesting an activated state. ATPase staining of epidermal sheet confirmed the decreased number of Langerhans cells. To clarify status of Langerhans cells, the activation of B7 was examined. Activation of B7-1 or B7-2 was not detected. Imiquimod, however, did enhance Langerhans cell migration from skin to draining lymph nodes. This enhanced Langerhans cell migration was also associated with an enhanced allergic contact hypersensitivity. These results suggest that the mechanism of modulation of immune response by imiquimod is in part due to effects on Langerhans cells.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Aminoquinolinas/farmacología , Células de Langerhans/efectos de los fármacos , Adenosina Trifosfatasas/metabolismo , Administración Tópica , Animales , Formación de Anticuerpos/efectos de los fármacos , Recuento de Células/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Citocinas/genética , Dermatitis por Contacto/fisiopatología , Células Epidérmicas , Antígenos de Histocompatibilidad Clase II/análisis , Imiquimod , Células de Langerhans/citología , Células de Langerhans/enzimología , Células de Langerhans/inmunología , Células de Langerhans/fisiología , Ratones , Ratones Endogámicos C57BL , ARN Mensajero/metabolismo , Regulación hacia ArribaRESUMEN
1alpha,25-Dihydroxyvitamin D3 (calcitriol) has been shown to inhibit the proliferation of peripheral blood mononuclear cells induced by allogeneic Langerhans cells in a human mixed epidermal cell lymphocyte reaction. The potent antigen-presenting function of Langerhans cells is gained during culture. We tried to dissect the effect of calcitriol on lymphocyte proliferation and Langerhans cell maturation in a murine mixed epidermal cell lymphocyte reaction using unfractioned epidermal cells as a source for Langerhans cells. First, calcitriol was added upon setup of the mixed epidermal cell lymphocyte reaction using cultured epidermal cells as antigen-presenting cells, and this was found to inhibit the proliferation of lymphocytes in a time- and concentration-dependent manner. When calcitriol was added only during preculture of freshly isolated epidermal cells, the subsequent mixed epidermal cell lymphocyte reaction was also inhibited. In addition, the growth of keratinocytes and the production of granulocyte/macrophage colony-stimulating factor during preculture of epidermal cells was completely inhibited. Supplementation with this growth factor only partially restored the proliferative response of lymphocytes. These results suggest that calcitriol inhibits both the alloantigen-driven stimulation of naive T cell and Langerhans cells maturation. Further experiments with purified Langerhans cells are required to elucidate the mechanism of action of calcitriol on Langerhans cell maturation.
Asunto(s)
Calcitriol/farmacología , Fármacos Dermatológicos/farmacología , Células de Langerhans/inmunología , Activación de Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Animales , Presentación de Antígeno/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Técnicas de Cocultivo , Humanos , Células de Langerhans/citología , Linfocitos/citología , Masculino , RatonesRESUMEN
Ultraviolet radiation (UVR), chemical carcinogens and contact sensitisers all reduce the density of Langerhans cells (LC) in murine epidermis; UVR also lowers the number of Thy-1 dendritic epidermal cells (Thy-1+ dEC). Topical application of all-trans retinoic acid (RA) renders these cells insensitive to UVR and the tumour promoter 12-0-tetradecanoylphorbol 13-acetate (TPA) but does not inhibit LC migration from the epidermis in response to a contact sensitiser. Additionally, when the diet of mice was supplemented with the retinoid temarotene, UVR was unable to reduce the number of LC or Thy-1+ dEC. Hence one of the anti-carcinogenic mechanisms of retinoids may be to protect LC from carcinogens.
Asunto(s)
Células de Langerhans/efectos de los fármacos , Neoplasias Experimentales/prevención & control , Tretinoina/administración & dosificación , Administración Cutánea , Animales , Recuento de Células/efectos de los fármacos , Recuento de Células/efectos de la radiación , Movimiento Celular/efectos de los fármacos , Células de Langerhans/citología , Células de Langerhans/efectos de la radiación , Rayos UltravioletaRESUMEN
Low doses (100 J/m2) of ultraviolet B (UVB) radiation from sunlamp fluorescent FS20 tubes inhibit the ability of freshly isolated murine epidermal Langerhans cells (LC) to support anti-CD3 MoAb-induced T-cell mitogenesis and selectively inhibit the upregulation of ICAM-1 expression by LC without causing appreciable cytotoxicity in short-term (less than or equal to 24 h) incubations (J Immunol 146:3347-3355, 1991). In the present study, epidermal cells (EC) were exposed to UVB radiation or were sham-irradiated and cultured for 24, 48, or 72 h when LC were recovered, enumerated, and assayed for simultaneous expression of I-A antigens and ICAM-1 by flow cytometry. UVB-irradiated LC that had been cultured for 24 h exhibited levels of I-A antigens comparable to those on unirradiated LC but expressed substantially less ICAM-1. After 48 and 72 h, cultured UVB-irradiated LC expressed somewhat lower levels of I-A antigens and markedly less ICAM-1 than unirradiated controls. Although similar numbers of LC were recovered from cultures initiated with UVB-irradiated and unirradiated epidermal cells after 24 h, far fewer identifiable LC were recovered from cultures seeded with irradiated cells at 48 and 72 h (approximately 50 and approximately 10% of control, respectively). The effect of UVB radiation on the survival of LC in vitro was not reversible with exogenous TNF alpha (125 U/ml) alone or granulocyte/macrophage colony-stimulating factor (5 ng/ml) and IL-1 (50 U/ml) in combination, although these cytokines had modest effects on the expression of I-A antigens and ICAM-1 by cultured UVB-irradiated LC. Results of survival studies performed with enriched LC preparations demonstrated that UVB radiation was clearly cytotoxic for LC and did not merely downregulate surface expression of I-A antigens or alter LC buoyant density. Exposure of LC to radiation from blacklight fluorescent (UVA) tubes (0.25 J/cm2) in the presence of 8-methoxypsoralen (1 micrograms/ml; PUVA) or monochromatic UVC radiation (20 J/m2) also inhibited LC accessory cell function. Results of survival studies performed with EC that had been exposed to PUVA or UVC radiation before culture were similar to those of studies performed with UVB-irradiated cells, although PUVA- and UVC-induced LC cytotoxicity was much more pronounced 48 h after culture initiation than UVB-induced cytotoxicity. UVA radiation alone augmented LC recovery at 24 and 48 h, but did not influence I-A antigen or ICAM-1 expression.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Células de Langerhans/efectos de la radiación , Rayos Ultravioleta , Animales , Células Presentadoras de Antígenos/fisiología , Células Presentadoras de Antígenos/efectos de la radiación , Moléculas de Adhesión Celular/genética , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Citocinas/farmacología , Relación Dosis-Respuesta en la Radiación , Femenino , Regulación de la Expresión Génica/efectos de la radiación , Antígenos de Histocompatibilidad Clase II/fisiología , Molécula 1 de Adhesión Intercelular , Células de Langerhans/citología , Ratones , Ratones Endogámicos BALB C , Terapia PUVARESUMEN
Although application of topical psoralen followed immediately by ultraviolet-A irradiation (non-interval PUVA) was reported to be effective in the treatment of psoriasis, its precise mechanisms of action have not yet been explored. Since regular topical PUVA therapy, consisting of the topical application of psoralen followed by UVA exposure 1-2 h later, can change the number and morphology of Langerhans cells (LCs) and inhibit contact hypersensitivity (CHS), we investigated whether these same effects may be induced by non-interval PUVA. Our results showed that no differences exist between these two types of PUVA treatment. Non-interval PUVA treatments of 3 J/cm2 produced no erythematous reactions and resulted in changes in the number and morphology of LCs. The non-interval regimen also inhibited CHS to dinitrofluorobenzene applied to the treated skin by inducing the suppressor lymphocytes. These results suggest that there might be a link between the observed changes of the LCs and the effectiveness of non-interval PUVA therapy in the treatment of psoriasis, through a mechanism other than the inhibition of DNA synthesis of psoriatic keratinocytes.
Asunto(s)
Dermatitis por Contacto/tratamiento farmacológico , Células de Langerhans/efectos de los fármacos , Terapia PUVA/métodos , Animales , Dermatitis por Contacto/inmunología , Femenino , Cobayas , Células de Langerhans/citología , Células de Langerhans/efectos de la radiación , Metoxaleno/administración & dosificación , Ratones , Ratones Endogámicos C3H , Terapia PUVA/efectos adversos , Dosis de Radiación , Factores de Tiempo , Rayos UltravioletaRESUMEN
A monoclonal antibody against CD-1(T6) was used for studies in the nasal mucosa of patients with isolated grass-pollen allergy to determine whether the number of CD-1-positive cells, presumably Langerhans cells, depends on the season in which the nasal biopsy is performed. An earlier study had demonstrated that during the grass-pollen season, there are significantly more CD-1-positive cells in nasal mucosa of patients with isolated grass-pollen allergy than in nonallergic control subjects without nasal complaints. During the grass-pollen season, the nasal epithelium of patients with an isolated grass-pollen allergy demonstrated significantly more CD-1-positive cells than before and after the season. Before and after the season, the number of CD-1-positive cells in epithelium of the allergic patients was not significantly greater than the corresponding number in epithelium of nonallergic subjects without nasal complaints.
Asunto(s)
Células de Langerhans/citología , Mucosa Nasal/citología , Polen , Rinitis Alérgica Estacional/patología , Adolescente , Adulto , Recuento de Células , Femenino , Humanos , Masculino , Persona de Mediana Edad , Poaceae , Factores de TiempoRESUMEN
The mechanism of irritant dermatitis and the immunologic consequences of such reactions are unclear. We evaluated the number and function of epidermal antigen-presenting cells contained in epidermal cell suspensions obtained from normal and irritant patch test reaction sites. Application of sodium lauryl sulfate or croton oil to human skin in vivo resulted in a progressive depletion in the number of epidermal OKT6+HLA-DR+ (T6+DR+) Langerhans cells (LC) from 3.1 +/- 0.2% of total epidermal cells (EC) to 1.2 +/- 0.1% after 8 d (mean values +/- SEM, N = 9). Between 1-4 d irritant patch test sites demonstrated an influx of non-Langerhans cell T6-DR+ cells. These cells were not DR+ keratinocytes but appeared to be of bone marrow derivation because they expressed the marker, HLe1. Among bone marrow derived cells, the T6-DR+EC appeared to be of monocyte, macrophage lineage, because they expressed the determinant recognized by the OKM5 (M5) antibody. Despite the induction of M5+DR+EC the total number of DR+EC showed progressively decreasing percentages over an 8-d period. Partial recovery to 73 +/- 12% of control value was observed at 2 weeks, with full recovery by 4 weeks after challenge. Concomitantly with the depletion of DR+EC, the capacity of EC to present alloantigens to T cells decreased. This reduction in antigen-presenting cell activity was strongly correlated to the reduction in total DR+ EC (r = 0.94, p less than 0.05). Thus, the capacity of irritants such as croton oil to abrogate the function of epidermal antigen-presenting cells may be related to the tumor promoting potential of these agents.
Asunto(s)
Células Presentadoras de Antígenos/fisiología , Irritantes , Neoplasias Cutáneas/inmunología , Piel/inmunología , Administración Cutánea , Adulto , Anciano , Células Presentadoras de Antígenos/inmunología , Aceite de Crotón/farmacología , Epidermis/inmunología , Antígenos HLA-DR/inmunología , Humanos , Irritantes/administración & dosificación , Células de Langerhans/citología , Células de Langerhans/inmunología , Células de Langerhans/fisiología , Leucocitos/inmunología , Persona de Mediana Edad , Piel/citología , Dodecil Sulfato de Sodio/farmacología , Linfocitos T/inmunología , Factores de TiempoRESUMEN
Monofunctional psoralens produce less phototoxicity than bifunctional psoralens after ultraviolet A (UVA) irradiation. We investigated the effect of repetitive treatments with angelicin (isopsoralen), a monofunctional psoralen, plus UVA radiation (IPUVA) on the number and morphology of dendritic epidermal cells (dEC). This effect was compared with that of 8-methoxypsoralen plus UVA radiation (PUVA), UVA alone, and UVB radiation. C3H/HeN mice were treated topically with the drugs three times/wk for 4 consecutive wk; followed each time by 1 or 2.5 J/cm2 of UVA radiation. Other groups of mice were treated with the drugs alone, UVA alone, or 0.81 J/cm2 of UVB. Epidermal sheets were stained for ATPase, Ia, and Thy-1 markers. Mice treated with PUVA and UVB exhibited severe phototoxicity, whereas no overt phototoxicity was observed in mice treated with IPUVA, UVA alone, or the drugs alone. Early during the PUVA and UVA treatments the ATPase marker was lost from dEC, followed by loss of the Ia marker; the Ia marker was lost before the ATPase marker from dEC in animals treated with IPUVA. At the end of the treatment, however, nearly total depletion of ATPase+, Ia+, and Thy-1+ dEC was observed in mice treated with PUVA and IPUVA. UVB radiation caused rapid depletion of Thy-1+ dEC as well as ATPase+ and Ia+ cells. During treatments with IPUVA, PUVA, UVA, and UVB, the Langerhans cells became rounded and lost their dendrites. These changes were quantitated by image analysis. We conclude that alterations of cutaneous immune cells can occur in the absence of overt phototoxicity, and that monofunctional and bifunctional psoralens plus low dose of UVA radiation may have different effects on dEC markers.
Asunto(s)
Células Dendríticas/efectos de los fármacos , Terapia PUVA , Adenosina Trifosfatasas/análisis , Animales , Antígenos de Superficie/análisis , Células Dendríticas/efectos de la radiación , Células Epidérmicas , Epidermis/enzimología , Epidermis/inmunología , Furocumarinas/uso terapéutico , Antígenos de Histocompatibilidad Clase II/análisis , Células de Langerhans/citología , Células de Langerhans/efectos de los fármacos , Células de Langerhans/efectos de la radiación , Metoxaleno/uso terapéutico , Ratones , Ratones Endogámicos , Trastornos por Fotosensibilidad/tratamiento farmacológico , Antígenos Thy-1 , Rayos UltravioletaRESUMEN
Long-standing hand and foot dermatoses, e.g. pustulosis palmoplantaris (PPP) and chronic eczematous hand dermatitis, severely affect the patients' quality of life. The cause of PPP is unknown and the disease usually responds unsatisfactorily to treatment. The aims of the studies of PPP were to determine the prevalence of thyroid disease and to evaluate the relative merits of treatment with etretinate, psoralen photochemotherapy (PUVA), and a combination of the two. Furthermore, epidermal Langerhans cells (LC) were quantified in lesional skin before and after treatment. The prevalence of thyroid disease was significantly increased in a group of PPP patients compared to normal individuals and psoriasis patients. Both hypo and hyperthyroidism were found. In addition, circulating autoantibodies to thyroid antigens were more common in patients with PPP than in the control group. The thyroid status was further examined in a new and larger group of PPP patients, including a 4-year follow-up examination of those with thyroid antibodies or subclinical thyroid dysfunction. The increased prevalence of thyroid diseases was corroborated when this PPP group was compared to an age and sex-matched control population sample from the same city. Some patients also showed biochemical evidence of gastric autoimmunity. Ninetyfour percent of the PPP patients were smokers at the time of onset of the skin disease, compared to 33% of the subjects in a control group. Patients with treatment-resistant PPP were recruited for a randomised, double-blind and placebo-controlled trial. A combination of etretinate and PUVA was more effective than monotherapy with etretinate or PUVA. The latter were equally effective. Etretinate frequently provoked side effects. Follow-up examinations showed a high relapse rate. Epidermal LC were visualised with monoclonal antibodies to Leu 6 and HLA-DR antigens utilizing an immunoperoxidase technique. Their number was increased in lesional skin. The number of HLA-DR positive LC was decreased following etretinate, and normalised with etretinate + PUVA. Chronic eczematous hand dermatitis is a common clinical challenge. These studies aimed at an evaluation of PUVA and UVB phototherapy in patients with recalcitrant lesions and to enumerate epidermal LC before and after treatment. PUVA was a highly effective mode of treatment and cleared all treated hands. UVB was better than no treatment but the dermatitis did not clear in any patient. The number of epidermal LC was increased in lesional palmar skin in both allergic contact dermatitis, irritant contact dermatitis and hyperkeratotic dermatitis of the palms.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Dermatitis por Contacto , Etretinato/administración & dosificación , Dermatosis del Pie , Dermatosis de la Mano , Células de Langerhans/citología , Terapia PUVA , Enfermedades Cutáneas Vesiculoampollosas , Enfermedades de la Tiroides/complicaciones , Adulto , Autoanticuerpos/análisis , Recuento de Células , Enfermedad Crónica , Ensayos Clínicos como Asunto , Dermatitis por Contacto/complicaciones , Dermatitis por Contacto/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Dermatosis del Pie/complicaciones , Dermatosis del Pie/tratamiento farmacológico , Dermatosis de la Mano/complicaciones , Dermatosis de la Mano/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Cutáneas Vesiculoampollosas/complicaciones , Enfermedades Cutáneas Vesiculoampollosas/tratamiento farmacológico , Fumar/efectos adversos , Glándula Tiroides/inmunología , Terapia UltravioletaRESUMEN
We studied the number and morphologic alterations of ATPase-positive Langerhans cells (LCs) in guinea pig epidermal sheets and also performed electron microscopic observations on them following long-term systemic psoralen photochemotherapy (PUVA) using 8-methoxypsoralen (8-MOP) and trimethylpsoralen (TMP). We con-firmed that the LCs are sensitive to PUVA treatment. The LC depleting effects of PUVA are dose-related and the restorator1 of LCs takes place by the 4th week following cessation of PUVA. Neither psoralens alone nor UVA alone showed any effects on LCs. There were no significant differences between 8-MOP and TMP when comparing the effects of 8-MOP plus UVA and TMP plus UVA on LC numbers and morphology. It seems that a moderate dose of PUVA causes an actual decrease in the number due to cell damage. Also, it appears likely that giant LCs appear during and following PUVA treatment as a compensatory process of the remaining cells.
Asunto(s)
Femenino , Animales , Recuento de Células , Cobayas , Células de Langerhans/citología , Metoxaleno/farmacología , Microscopía Electrónica , Terapia PUVA , Trioxsaleno/farmacologíaRESUMEN
The Langerhans cell system including the Langerhans cell (LC), the indeterminate epidermal cell, the lymphoid interdigitating cell, and the lymph veiled cell is nowadays considered as a very peculiar subpopulation of the mononuclear phagocyte system. The authors have tried in this review to point out the main salient features, the qualitative and quantitative variations of these cells during physiological, experimental and pathological processes.