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Biomedical subjects

Peter Fritsch

Publications and source records attributed to Peter Fritsch.

21 records · Page 2Linked to original sources
PubMed2002

Adhesion of dendritic cells derived from CD34+ progenitors to resting human dermal microvascular endothelial cells is down-regulated upon maturation and partially depends on CD11a-CD18, CD11b-CD18 and CD36.

DC are sentinels of the immune system. In order to reach the skin, bone-marrow-derived DC precursors need to bind and migrate through microvascular endothelial cells. Binding of DC toprimary endothelial cells of the skin has not been investigated. We therefore determined adhesion of DC at different stages of development to human dermal microvascular endothelial cells (HDMEC). DC were derived from CD34+ progenitors in cord blood. To enhance DC maturation, a defined cocktail of IL-1beta+IL-6+TNF-alpha+PGE2 was applied. Adhesion was quantified by fluorimetric and phase-contrast microscopical assays. Significantly more DC precursors (tested on day 5 after isolation) than mature DC (spontaneously matured or cytokine-cocktail-matured and tested on day 13) bound to unstimulated HDMEC. In contrast, the maturation stage of DC had no influence on their binding to human umbilical vein endothelial cells. Pretreatment of HDMEC with TNF-alpha and IFN-gamma resulted in an enhanced attachment of both DC precursors and mature DC. Mature DC lacked expression of CD31, CD36, CD45RA and CLA, and expressed lower levels of CD11a, CD11b and CD49d as compared with precursors tested on day 5. mAb against CD18, CD11a, CD11b, and CD36 markedly inhibited DC binding, whereas anti-CLA, anti-DC-SIGN, anti-CD29 and anti-CD49 mAb did not. Our data support the hypothesis of immunosurveillance with selective recruitment of blood DC precursors to resting and, more so, to inflamed skin. The data have potential relevance for anti-cancer immunotherapy strategies favoring the intracutaneous application of mature DC.

Antigens, CD34↗
PubMed2002

Dendritic cells contribute to the development of atopy by an insufficiency in IL-12 production.

BACKGROUND: IL-12 is a crucial factor in the development and course of allergic diseases. By virtue of their IL-12 production, dendritic cells (DCs) are potent inducers of T(H)1 responses. However, distinct subsets of DCs have also been shown to induce T(H)2 differentiation. OBJECTIVE: We hypothesized that DCs from atopic and nonatopic individuals might differ in their propensity to skew T-cell responses to either the T(H)1 type or the T(H)2 type. To this end, we investigated the cytokine patterns produced by DCs from atopic and nonatopic individuals, and we attempted to clarify whether this could be due to different DC lineages or, alternatively, to different microenvironmental factors. METHODS: DCs were generated from lymphocyte-depleted PBMCs from atopic and nonatopic donors and fully matured with monocyte-conditioned medium. Production of IL-4, IL-5, IL-10, IL-12, and IL-13 in response to CD40 ligation was measured with ELISA. DC subsets were identified in PBMCs from freshly drawn blood by 3-color flow cytometry. RESULTS: Compared with DCs from healthy donors, monocyte-derived DCs from atopic patients produced less bioactive IL-12 and IL-10. DC production of IL-4, IL-13, and IL-5 was not detected. Relatively more CD123(+) DCs, corresponding to T(H)2-inducing "DC2s," were found in PBMCs from atopic patients. CONCLUSION: The data suggest that in addition to the described abnormalities in the patients' T-cell populations, DCs might also critically contribute to the atopic/allergic T(H)1 outcome in the patient and thus to the disease.

Adult↗