FoxP3-Positive Cells and Their Contacts with Mast Cells Are Highly Increased in Basal Cell Carcinoma.

INTRODUCTION: The cells of the immune system are thought to contribute to the development of skin cancers, such as basal cell carcinoma (BCC). One possible mechanism may be the interaction between mast cells and regulatory T cells (Tregs), resulting in immunosuppression. METHODS: Fresh-frozen biopsies from the lesional and nonlesional skin of 16 patients with BCC were processed for the enzymehistochemical staining of mast cell tryptase, immunohistochemical staining of FoxP3 (a marker of Tregs) as well as for the double-staining method to label tryptase+ cells and FoxP3+ cells on the same cryosection. The cell numbers and apparent morphological contacts (AMCs) between these cell types were counted. RESULTS: There was a high increase in the number of tryptase+ cells, FoxP3+ cells, and AMCs between them in the lesional compared to corresponding nonlesional skin (p < 0.0001) in all cases. CONCLUSION: A morphological basis is theoretically present in BCC, suggesting an immune evasive microenvironment.

CD40 Ligand Is Increased in Mast Cells in Psoriasis and Actinic Keratosis but Less So in Epithelial Skin Carcinomas.

The expression of CD40 ligand (CD40L) in mast cells was investigated in biopsies from lesional and non-lesional skin samples of patients with psoriasis, actinic keratosis (AK), basal cell carcinoma, and squamous cell carcinoma using a sequential double-staining technique. The percentage of CD40L+ mast cells was higher in the lesional than in the non-lesional skin (p < .003). Interestingly, this percentage was lower in both carcinomas than in psoriasis and actinic keratosis (p < .025). Cells immunopositive for CD40 receptor were increased in all lesion types but especially so in carcinomas. The results suggest a dysregulated anti-tumoral immune response by mast cell CD40L in skin carcinomas.

Increased numbers of tryptase-positive mast cells in the healthy and sun-protected skin of tobacco smokers.

BACKGROUND: Tobacco smoking may cause skin aging through mast cell proteinases. OBJECTIVE: To compare the numbers of mast cells showing tryptase and chymase in the healthy-looking skin of smokers and non-smokers. METHODS: The study subjects consisted of 80 males, 42 of whom were smokers and 38 non-smokers. A skin biopsy from the medial arm was processed for immunohistochemical staining of tryptase and chymase, as well as chymase inhibitors alpha-1-proteinase inhibitor (alpha-1-PI) and alpha-1-antichymotrypsin (alpha-1-AC). RESULTS: The number of tryptase(+) mast cells was significantly higher in the smoker group (84 ± 32 cells/mm(2)) than in the non-smoker group (70 ± 32 cells/mm(2)) (p = 0.044). Likewise, the number of chymase(+) mast cells was higher in the smoker group (89 ± 20 vs. 80 ± 22 cells/mm(2)), though statistical significance was not reached (p = 0.07). No significant difference was observed in alpha-1-PI(+) and alpha-1-AC(+) cells. CONCLUSION: Especially tryptase, but probably also chymase, may have an influence on the skin of smokers, such as wrinkling and aging.

Quantitative analysis of collagen network structure and fibril dimensions in cartilage repair with autologous chondrocyte transplantation.

OBJECTIVE: The aim of this study was to undertake a stereological analysis to quantify the dimensions of the collagen network in the repair tissue of porcine joints after they had been subjected to autologous chondrocyte transplantation (ACT). METHOD: ACT was used to repair cartilage lesions in knee joints of pigs. Electron-microscopic stereology, immunostaining for type II collagen, and quantitative polarized-light microscopy were utilized to study the collagen fibrils in the repair tissue 3 and 12 months after the operation. RESULTS: The collagen volume density (V(V)) was lower in the repair tissue than in normal cartilage at 3 months (20.4 vs. 23.7%) after the operation. The collagen surface density (S(V), 1.5·10(-2) vs. 3.1·10(-2) nm(2)/nm(3)) and V(V) increased with time in the repair tissue (20.4 vs. 44.7%). Quantitative polarized-light microscopy detected a higher degree of collagen parallelism in the repair tissue at 3 months after the operation (55.7 vs. 49.7%). In contrast, 1 year after the operation, fibril parallelism was lower in the repair tissue than in the control cartilage (47.5 vs. 69.8%). CONCLUSION: Following ACT, V(V) and S(V) increased in the repair tissue with time, reflecting maturation of the tissue. One year after the operation, there was a lower level of fibril organization in the repair tissue than in the control cartilage. Thus, the newly synthesized collagen fibrils in the repair tissue appeared to form a denser network than in the control cartilage, but the fibrils remained more randomly oriented.

Immunoreactivity to CYP24A1, but not vitamin D receptor, is increased in mast cells of keratinocyte skin cancers.

In mouse skin models, mast cells have been shown to express vitamin D receptor (VDR) that can mediate the immunosuppressive effects of ultraviolet B radiation and vitamin D3. However, VDR activation leads to the expression of CYP24A1, a hydroxylase that can inactivate vitamin D3 metabolites. To examine immunoreactivity to VDR and CYP24A1 in mast cells from normal human skin, keratinocyte skin cancers, and disorders of chronic inflammation. Frozen biopsies were collected from the non-lesional and lesional skin of patients with actinic keratosis (AK), Bowen's disease/squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and psoriasis. The expression of VDR and CYP24A1 in tryptase-positive mast cells was analysed using double-staining methods. Less than 0.5% of the mast cells were immunoreactive to VDR in both the non-lesional and lesional skin for all disease groups. In non-lesional skin, only 0.5-2.9% of the mast cells were immunopositive for CYP24A1, however, the percentage of mast cells containing CYP24A1 was significantly increased in lesional skin of AK, SCC, and BCC. In contrast to human skin, LAD2 mast cells cultured from a patient with mast cell sarcoma/leukaemia revealed that about 34% and 6.5% of the cells were immunopositive for VDR and CYP24A1, respectively. Whereas a very small proportion of mast cells in human skin express VDR and CYP24A1, the proportion of mast cells expressing CYP24A1 in keratinocyte skin cancers is increased; the mechanism underlying this is unclear.

Mast cells express CYP27A1 and CYP27B1 in epithelial skin cancers and psoriasis.

BACKGROUND: Ultraviolet (UV) radiation and the vitamin D system are involved in immunosuppression in the skin. Previous in vitro and animal studies suggest a role for mast cells in these mechanisms. OBJECTIVES: To study vitamin D3 metabolizing enzymes, CYP27A1 and CYP27B1, in mast cells in epithelial skin cancers and psoriasis. MATERIALS AND METHODS: Biopsies were collected from the non-lesional and lesional skin of patients with actinic keratosis (AK), Bowen's disease/squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and psoriasis. CYP27A1 and CYP27B1 in mast cells were analysed using a sequential double-staining method. RESULTS: The percentage of mast cells containing CYP27A1 was significantly higher in lesional than non-lesional skin in all diseases, especially in SCC and BCC. In addition, the percentage of mast cells containing CYP27B1 was significantly increased in BCC, AK, and psoriatic lesions as well. Interestingly, only about 5-6% and 2% of the mast cells expressed CYP27A1 and CYP27B1, respectively, in the non-lesional skin of psoriatic and AK patients. In contrast, 23-38% and 6-9% of the mast cells were immunopositive for CYP27A1 and CYP27B1, respectively, in the non-lesional skin of BCC and SCC patients. In human LAD2 mast cell cultures, about 30% and 15% of the mast cells showed CYP27A1 and CYP27B1, respectively, though the immunostainings of these enzymes were not markedly affected by UVB irradiation. CONCLUSION: Increased proportions of mast cells express vitamin D3 metabolizing enzymes in the lesional skin. Therefore, mast cells may promote an immunosuppressive environment, e.g., in skin carcinoma.