RESUMO
In contrast to resident constitutive mast cells (CMCs), mucosal MCs (MMCs) appear in the lung and trachea of sensitized mice only following inhalation challenge. We monitored the influx and maturation of MCs by their expression of Kit, FcÉRI, ß7-integrin and side scatter (SSC) by flow cytometry. Influx of MC progenitors (MCps) (FcÉRI(lo), Kit(int), ß7(hi), and SSC(lo)) peaks 1 day after challenges and subsides to baseline by day 7 after challenge. The mature MMCs appear as a distinct population on day 7 and peak at day 14 with higher SSC and FcÉRI expression, but lower ß7 and Kit expression. A distinct transitional population is present between 1 and 7 days after challenge. Maturation occurs more rapidly in the trachea. The resident tracheal CMCs had higher SSC, FcÉRI, and Kit and lower ß7-integrin expression than the MMCs. By histology, the MMCs follow similar kinetics to the flow cytometry-identified mature MMCs and are notably persistent for >42 days. Steroid treatment reduced inflammation and MCp influx but had no effect on established MMCs. Thus, changes in SSC, FcÉRI, and Kit together with the expression of αE/α4:ß7-integrins characterizes the development of induced MMCs from MCps and distinguishes them from resident CMCs in the trachea and large airways.
Assuntos
Mastócitos/imunologia , Pneumonia/imunologia , Hipersensibilidade Respiratória/imunologia , Células-Tronco/imunologia , Traqueia/imunologia , Animais , Anti-Inflamatórios/farmacologia , Diferenciação Celular , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Cadeias beta de Integrinas/genética , Cadeias beta de Integrinas/imunologia , Mastócitos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Pneumonia/genética , Prednisona/farmacologia , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/imunologia , Receptores de IgE/genética , Receptores de IgE/imunologia , Hipersensibilidade Respiratória/induzido quimicamente , Hipersensibilidade Respiratória/tratamento farmacológico , Hipersensibilidade Respiratória/genética , Transdução de Sinais , Células-Tronco/patologia , Traqueia/patologiaAssuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Dessensibilização Imunológica , Toxidermias/etiologia , Eritema/induzido quimicamente , Prurido/induzido quimicamente , Adalimumab , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Dessensibilização Imunológica/métodos , Difenidramina/uso terapêutico , Relação Dose-Resposta a Droga , Toxidermias/diagnóstico , Toxidermias/tratamento farmacológico , Toxidermias/terapia , Famotidina/uso terapêutico , Feminino , Humanos , Injeções Subcutâneas , Testes Intradérmicos , Testes Cutâneos , Fatores de TempoRESUMO
BACKGROUND: Animal models are important tools for studies in skin physiology and pathophysiology. Due to substantial differences in skin characteristics such as thickness and number of adnexa, the results of animal studies cannot always be directly transferred to the human situation. Therefore, transplantation of human skin on to SCID (severe combined immunodeficiency) mice might offer a promising tool to perform studies in viable human skin without the direct need for human volunteers. OBJECTIVES: To characterize the physiological and anatomical changes of a human skin transplant on a SCID animal host. METHODS: In this study human skin was transplanted on to 32 SCID mice and followed for 6 months. Barrier function was assessed by transepidermal water loss (TEWL; tewametry) and moisture content of the stratum corneum was studied by measurement of electrical capacitance (corneometry). RESULTS: The results showed considerable deviations of TEWL values and skin hydration between the grafts and human skin in vivo. The human skin showed epidermal hyperkeratosis and moderate sclerosis of the corium 4 and 6 months after transplantation on to SCID mice. CONCLUSIONS: Our results indicate that human skin does not completely preserve its physiological and morphological properties after transplantation on to SCID mice. Therefore, results from experiments using this model system need to be discussed cautiously.
Assuntos
Modelos Animais de Doenças , Transplante de Pele/patologia , Transplante Heterólogo/patologia , Animais , Água Corporal/metabolismo , Capacitância Elétrica , Epiderme/metabolismo , Epiderme/fisiologia , Feminino , Humanos , Camundongos , Camundongos SCID , Transplante de Pele/fisiologia , Transplante Heterólogo/fisiologia , Perda Insensível de ÁguaRESUMO
BACKGROUND: Cutaneous exposure to a variety of irritants has been extensively studied in recent years. Nevertheless, knowledge of the induction of irritant dermatitis, especially by mild irritants at low doses and for a short duration of exposure, is still incomplete. OBJECTIVES: To quantify the irritant effects and barrier disruption properties of ascorbic acid (ASC), acetic acid (ACA) and sodium hydroxide (NaOH), particularly in combination with an anionic detergent, sodium lauryl sulphate (SLS). METHODS: In a tandem repeated irritation test, the irritants were applied for 30 min twice daily for 4 days to the skin of the mid-back of 19 healthy volunteers of both sexes. We used bioengineering techniques for measurement of transepidermal water loss (TEWL) and skin colour reflectance, as well as visual scoring. RESULTS: Repeated application of ASC and ACA caused a moderate increase in TEWL and erythema. The sequential application of ASC or ACA and SLS enhanced these effects. NaOH induced a strong reaction when applied both occlusively and nonocclusively as well as in combination with SLS, with an early onset of the inflammatory signs, leading to discontinuation of the application on the third day in most of the test fields. Notably, the irritant effect of NaOH was not as marked when applied sequentially with SLS. CONCLUSIONS: Our results demonstrate that concurrent application of an anionic detergent and a mild acidic irritant can lead to disruption of the barrier function which, although not additive, is still considerable. The combined application of SLS and mild acids does not prevent SLS-induced irritation. Furthermore, we showed that NaOH in low concentrations may also act as a potent irritant but that its effect is not enhanced by SLS. The necessity of adequate skin protection and reduction of contact with substances that are potentially barrier disruptive and irritant, e.g. in the food industry, is emphasized, not only when handling detergents, but also when processing food products.