Decrease In Langerhans Cell Density Research Articles

The Effect of Autologous Platelet Lysate Eye Drops: An In Vivo Confocal Microscopy Study.

Purpose. To determine the effectiveness of autologous platelet lysate (APL) eye drops in patients with primary Sjögren syndrome (SS) dry eye, refractory to standard therapy, in comparison with patients treated with artificial tears. We focused on the effect of APL on cornea morphology with the in vivo confocal microscopy (IVCM). Methods. Patients were assigned to two groups: group A used autologous platelet lysate QID, and group B used preservative-free artificial tears QID, for 90 days. Ophthalmological assessments included ocular surface disease index (OSDI), best corrected visual acuity (BCVA), Schirmer test, fluorescein score, and breakup time (BUT). A subgroup of patients in group A underwent IVCM: corneal basal epithelium, subbasal nerves, Langerhans cells, anterior stroma activated keratocytes, and reflectivity were evaluated. Results. 60 eyes of 30 patients were enrolled; in group A (n = 20 patients) mean OSDI, fluorescein score, and BUT showed significant improvement compared with group B (n = 10 patients). The IVCM showed a significant increase in basal epithelium cells density and subbasal nerve plexus density and number and a decrease in Langerhans cells density (p < 0.05). Conclusion. APL was found effective in the treatment of SS dry eye. IVCM seems to be a useful tool to visualize cornea morphologic modifications.

Langerhans Cell Density in Cervical Intraepithelial Neoplasia Associated With Human Papillomavirus Infection in HIV-Infected and HIV-Noninfected Brazilian Women

Local immunity plays an important role in the cervical defense mechanisms that prevent the development of cervical intraepithelial neoplasia. The objective of this study was to determine the involvement of local immunity by evaluating Langerhans cell (LC) density in cervical biopsies of human immunodeficiency virus (HIV)-positive and HIV-negative women. A cross-sectional study was developed by including HIV-positive and HIV-negative women. All patients presented human papillomavirus DNA from the uterine cervix, which was detected by polymerase chain reaction or hybrid capture II. Cervical biopsies were assessed for LC density and cervical intraepithelial neoplasia. Langerhans cells were identified by immunohistochemistry using anti-CD1a and anti-S100 antibodies. Associations among cervical LC density, the type of cervical lesion, CD4 lymphocyte count, and HIV viral load were analyzed using logistic regression (SPSS, version 12.0). Seventy-seven women (40 seropositive and 37 seronegative) were enrolled. The mean ± SD LC density identified with the anti-CD1a antibody was 0.80 ± 0.7 cells versus 2.6 ± 1.6 cells (P < 0.0001), whereas the mean ± SD LC density identified by the anti-S100 antibody was 1.3 ± 1.0 cells versus 3.6 ± 1.7 cells (P < 0.0001) among the HIV-positive and HIV-negative women, respectively. There were no associations between LC density and HIV viral load, CD4 lymphocyte count, or human papillomavirus genotype (P > 0.05). In a logistic regression model, HIV infection was the only factor independently associated with a decrease in LC density. Human immunodeficiency virus infection was found to be an independent factor that explains the decrease in local immunity in the uterine cervix, which could allow the development of cervical lesions. This effect was not associated with CD4 lymphocyte count or HIV viral load.

Acral lesions of vitiligo: why are they resistant to photochemotherapy?

Acral lesions of vitiligo are usually resistant to conventional lines of treatment as well as surgical interventions. To clarify causes underlying resistance of acral lesions to pigmentation in vitiligo by studying some of the factors associated with mechanisms of repigmentation following photochemotherapy. The study included twenty patients with active vitiligo. Skin biopsies were taken from lesional and perilesional skin of areas expected to respond (trunk and proximal limb) and skin of acral areas, before and after PUVA therapy. Sections were stained with H and E, Melan-A, MHCII, CD1a, SCF and c-kit protein. Before treatment acral areas showed significantly lower hair follicle density, melanocyte density, Langerhans cell (LC) density, epidermal MHCII expression, lesional SCF expression and perilesional c-kit expression. Following treatment with PUVA in both non-responsive acral and repigmenting non-acral lesions identical immunohistochemical changes in the form of significant decrease in LC density, epidermal MHC-II and SCF expression were observed. The surprisingly similar histochemical changes in response to PUVA in acral and non-acral lesions did not manifest with clinical repigmentation except in non-acral ones. Factors such as inherent lower melanocyte density, lower melanocyte stem cell reservoirs and/or lower baseline epidermal stem cell factor may be considered as possible play makers in this respect.

Clinical evidence of benefits of a dietary supplement containing probiotic and carotenoids on ultraviolet-induced skin damage

Lactobacillus johnsonii (La1) has been reported to protect skin immune system homeostasis following ultraviolet (UV) exposure. To assess the effects of a dietary supplement (DS) combining La1 and nutritional doses of carotenoids on early UV-induced skin damage. Three clinical trials (CT1, CT2, CT3) were performed using different UV sources: nonextreme UV with a high UVA irradiance (UV-DL, CT1), extreme simulated solar radiation (UV-SSR, CT2) and natural sunlight (CT3). All three clinical trials were carried out in healthy women over 18 years of age with skin type II-IV. In CT1, early markers of UV-induced skin damage were assessed using histology and immunohistochemistry. In CT2, the minimal erythemal dose (MED) was determined by clinical evaluation and by chromametry. Chromametry was also used to evaluate skin colour. Dermatologists' and subjects' assessments were compiled in CT3. A 10-week DS intake prevented the UV-DL-induced decrease in Langerhans cell density and the increase in factor XIIIa+ type I dermal dendrocytes while it reduced dermal inflammatory cells. Clinical and instrumental MED rose by 20% and 19%, respectively, and skin colour was intensified, as shown by the increase in the ΔE* parameter. The efficacy of DS was confirmed by dermatologists and subjects under real conditions of use. Nutritional supplementation combining a specific probiotic (La1) and nutritional doses of carotenoids reduced early UV-induced skin damage caused by simulated or natural sun exposure in a large panel of subjects (n=139). This latter result might suggest that DS intake could have a beneficial influence on the long-term effects of UV exposure and more specifically on skin photoageing.

Oleic acid, a skin penetration enhancer, affects Langerhans cells and corneocytes

Permeation enhancers (PE) are frequently used in the field of dermal research and for the development of transdermal delivery products. However, their influence on skin epidermal Langerhans cells (LC) has not yet been investigated. In this work we studied the effect of four PE, oleic acid (OA), propylene glycol (PG), ethanol, and diethylene glycol monoethyl ether (DGME), and an iontophoretic treatment on the morphometric parameters of epidermal Langerhans cells (LC). Retinoic acid (RA) was used as a positive control. Test solutions were applied to the footpad of Sabra mice. The area, perimeter, density and shape factor (SF) were the morphometric parameters evaluated following ATPase staining of LC. Application of RA led to a large decrease in cell density (−50.2%, P<0.01) and dendritic shape (19.8%, P<0.01). Treatment with 10% OA in ethanolic solution caused a severe decrease in LC density (−69.0%, P<0.01), accompanied by a decrease in dendricity as measured by the changes in SF. Ethanol had no statistically significant effect on the LC morphologic parameters tested. All other PE had a mild, if any, effect on LC morphology. SEM micrographs of the skin of IOPS hairless rats demonstrated that 24 h in vivo treatment with 10% OA in ethanolic solution resulted in the generation of pores on the surface of epidermal corneocytes.

Counts and areas of S-100-positive epidermal dendritic cells in atypical molluscum contagiosum affecting HIV+ patients.

Molluscum contagiosum is a common and self-limiting viral infection, that in HIV+ patients courses as an opportunist affection with atypical clinical features. Impaired cell-mediated immune response could be involved in such atypical growth. We evaluated the density and area of Langerhans cells (LC) using S-100 immunohistochemistry in seven atypical molluscum contagiosum. LC density was quantified by three different methods using computer-assisted morphometry as well as estimating the relative area of LC with respect to epidermal area. Results were compared with two control groups (normal skin specimens and molluscum contagiosum affecting non-AIDS healthy patients). We found a virtual absence of LC in areas of molluscum lesions affecting both HIV+ and non-AIDS patients. Likewise we observed an evident decrease in LC density in perilesional epidermis of atypical molluscum with respect to both control groups. Upon comparing the counts and areas, we observed that this reduction in LC count was statistically significant only when considering LC related to length of basement membrane in atypical molluscum with respect to normal skin specimens. Our finding of a reduced number of LC in the perilesional epidermis of HIV+ patients with atypical molluscum could explain the high frequency and clinical challenge of molluscum contagiosum in immunocompromised people. In spite of these results, further studies of LC kinetics and functions are required to precisely elucidate their role in the course of molluscum contagiosum in HIV+ patients.

The steady-state turnover of murine epidermal Langerhans cells.

We have investigated the steady-state turnover of murine epidermal Langerhans cells (LCs) using an X-irradiation model, 3H-thymidine autoradiography and cultured epidermal sheet explants, and by assessing the LC population in normal mice. The LC density after whole-body irradiation without any cutaneous shielding was not significantly different from that in skin shielded during whole-body irradiation (P > 0.05), indicating that the additional irradiation to the skin did not contribute to a decrease in LC density. In both instances, the LC number gradually decreased in a linear fashion. The results indicate that epidermal LCs continuously leave the epidermis and are continually replaced by circulating precursor cells from the bone marrow at a steady rate. Autoradiographic studies after a pulse injection of 3H-thymidine showed a labelling index of 0.013%, indicating that local mitosis is not an important contributor to the maintenance of the epidermal LC population. Although local X-irradiation resulted in temporary reduction of LC density, epidermal sheet explant culture obtained immediately after local X-irradiation showed no difference in LC density as compared with control unirradiated skin, indicating that the decrease in LC density was not due to significant LC destruction. From these data, we calculated that the half-life of murine LCs in the epidermis is approximately 9 days.

Langerhans cells in vaccinia virus infection in mouse skin

Langerhans cells function as potent antigen-presenting cells in the epidermis. They were shown to play an essential role in the mechanisms of defense of the skin against viral infections. In the present study, the response of Langerhans cells to infection of the skin with vaccinia virus was investigated. Decrease in Langerhans cell density in the skin was accompanied by an increase in the pathogenicity of the WR and Noguchi but not of the Lister strain of vaccinia virus. Langerhans cell density was shown to increase rapidly at the site of inoculation with the two pathogenic strains of vaccinia virus.

Effect of Systemic and Topical Application of Testosterone Propionate on the Density of Epidermal Langerhans Cells in the Mouse

Epidermal Langerhans cells (LCs) are bone marrow-derived immune cells in the epidermis. Recently, we reported that adenosine triphosphatase (ATPase)-positive LC density in the hind-limb skin of male mice was lower than that of female and that orchiectomy resulted in an increase in LC density, though ovariectomy had no significant effect. To further investigate the control mechanisms of sex differences in LC density, the effect of systemic and topical application of testosterone propionate (TP) on LC density was examined in C57BL/6 mice. Subcutaneous injections of TP 5.8 X 10(-8) mol (20 micrograms)/day/mouse for 14 d resulted in a significant decrease in LC density both in orchiectomized males and normal females, and such an effect was also observed in adrenalectomized mice, suggesting that this effect of TP is not indirectly mediated by glucocorticosteroids. TP was also effective when applied as an ointment (1% or 5%) to the right hind-limb skin of both orchiectomized males and normal females for 14 d; namely, the LC density of the right hind-limb was lower than that of the left. Beta-estradiol and progesterone 5.8 X 10(-8) mol/day/mouse had no significant effect on LC density when systemically applied for 14 d to normal males and females. These results suggest that sex differences in LC density may result from higher concentrations of testosterone or its metabolites in males, and that the function of testosterone may be local.

Alpha Tocopherol Alters the Distribution of Langerhans Cells in DMBA-treated Hamster Cheek Pouch Epithelium

Thirty-seven adult male and female golden hamsters (Mesocricetus auratus) were divided into four experimental groups. In Group A, the animals served as untreated controls, having the left buccal pouches painted with mineral oil. In Group B, the animals received 10 mg vitamin E (alpha tocopherol) in peanut oil by the oral route, with a fine pipette, twice weekly. In Group C animals, the left buccal pouch was painted three times weekly with DMBA (0.5% solution of 7,12 dimethylbenz(a)anthracene in heavy mineral oil). Group D animals received both vitamin E and DMBA in the amounts indicated for Groups B and C, with the vitamin E being administered on days alternate to the DMBA painting, also in the manner described for the above groups. All animals were killed after eight weeks of treatment. Epithelial whole mounts were prepared from the left buccal pouches. These specimens were then stained for ATPase to demonstrate the presence of Langerhans cells (LCs). A notably decreased density of LCs was observed after treatment with DMBA. Vitamin E administration in addition to DMBA treatment resulted in a less dramatic decrease in LC density. Since vitamin E has been shown to retard experimental oral carcinogenesis, vitamin E may retard carcinogenesis by maintaining the number of Langerhans cells.