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Biomedical subjects

M Leverkus

Publications and source records attributed to M Leverkus.

21 records · Page 2Linked to original sources

Effect of chronic wound fluid on fibroblasts.

This study examines how the microenvironment created by fluid in chronic wounds influences the growth of dermal fibroblasts. Newborn fibroblasts, which are known to grow rapidly, were used as a model system to explore how chronic wound fluid affects the growth of regenerative fibroblasts. Wound fluid was collected from patients with chronic venous leg ulcers (duration longer than two months). The biological properties of this fluid were then further characterised to elucidate its molecular effects on cell growth. Results indicate that chronic wound fluid dramatically inhibited the growth of newborn dermal fibroblasts. This growth inhibitory effect was variable among donors, reversible and heat-sensitive. The inhibitory effect was due not to cytotoxicity or impaired plating efficiency of these cells, but to specific interference with the cell cycle. Chronic wound fluid arrested newborn fibroblast growth by preventing entry into the S-phase, or DNA synthesis-phase, of the cell cycle. In contrast to its effects on newborn fibroblasts, chronic wound fluid either stimulated or had a minimal effect on fibroblasts which had been cultured from the edge of chronic venous leg ulcers and healthy tissue on the upper thigh in the same patient. This may partially account for the impaired healing seen in chronic venous leg ulcers.

Adult↗

Fas/Fas ligand interaction contributes to UV-induced apoptosis in human keratinocytes.

Keratinocytes in human skin undergo apoptosis during various inflammatory processes and after ultraviolet (UV) irradiation. To determine if keratinocyte apoptosis may be mediated by the Fas/APO-1 receptor (CD95), a signal transduction pathway known to initiate programmed cell death of lymphocytes, we investigated Fas expression, modulation, and function in keratinocytes. Keratinocytes constitutively expressed the 2.5- and 1.9-kb Fas transcripts, as well as the 43-kDa Fas protein. Treatment of interferon-gamma-stimulated keratinocytes with Fas agonistic antibody significantly promoted their cell death, indicating that Fas in keratinocytes is functional. UV irradiation induced Fas mRNA expression within 16 to 24 h and Fas protein within 24 h and through 48 h after irradiation. Furthermore, keratinocytes constitutively expressed Fas ligand (FasL) mRNA and protein. UV irradiation induced FasL mRNA as early as 4 h after irradiation and elevated FasL mRNA levels were maintained for at least 24 h postirradiation. Moreover, a FasL neutralizing antibody significantly reduced UV-induced apoptosis of IFN-gamma-treated keratinocytes. Our data strongly suggest that the Fas system contributes to keratinocyte apoptosis in UV-irradiated human skin.

Antibodies, Monoclonal↗

Elevated serum levels of interleukin-10 in patients with metastatic malignant melanoma.

Interleukin-10 (IL-10), originally described as a product of TH2 cell clones, has been recognized as a potential immunosuppressive cytokine. To investigate the relevance of IL-10 in melanoma patients in vivo, we studied IL-10 serum levels in 104 untreated patients in different stages of the disease; 20 healthy subjects and 22 patients with inflammatory dermatoses served as controls. Serum levels were measured by ELISA. Only one of 31 patients with stage I melanoma (3%) and one of 16 stage II patients (6%) showed detectable IL-10 levels. Interestingly, six of 17 patients with lymph node metastases (stage III, 35%) and 29 of 40 patients with widespread disease (stage IV, 73%) revealed IL-10 levels of 15-480 pg/ml. No healthy person and only one control patient had a detectable IL-10 serum level. The data suggest that IL-10 in melanoma patients may contribute to down-modulation of anti-tumour responses in vivo.

Adult↗