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C Winzler

Publications and source records attributed to C Winzler.

7 recordsLinked to original sources

Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures.

The signals controlling the checkpoints of dendritic cells (DC) maturation and the correlation between phenotypical and functional maturational stages were investigated in a defined model system of growth factor-dependent immature mouse DC. Three sequential stages of DC maturation (immature, mature, and apoptotic) were defined and characterized. Immature DC (stage 1) had low expression of costimulatory molecules, highly organized cytoskeleton, focal adhesion plaques, and slow motility; accordingly, they were very efficient in antigen uptake and processing of soluble proteins. Further, at this stage most of major histocompatibility complex class II molecules were within cytoplasmic compartments consistent with a poor allostimulatory capacity. Bacteria or cytokines were very efficient in inducing progression from stage 1 towards stage 2 (mature). Morphological changes were observed by confocal analysis including depolymerization of F-actin and loss of vinculin containing adhesive structures which correlates with acquisition of high motility. Antigen uptake and presentation of native protein antigen was reduced. In contrast, presentation of immunogenic peptides and allostimulatory activity became very efficient and secretion of IL-12 p75 was detectable after antigen presentation. This functional DC maturation ended by apoptotic cell death, and no reversion to the immature phenotype was observed.

Animals↗

Bacteria and bacterial cell wall constituents induce the production of regulatory cytokines in dendritic cell clones.

The primary function of dendritic cells (DC) is the uptake, processing, and presentation of antigens to unprimed T cells, but the regulation of these functions is largely unknown. The study of the signals that maintain DC in a resting state or that drive their activation has been hampered by the difficulties in obtaining pure DC populations. The availability of immortalized DC clones from different tissues (spleen and skin) allowed us to investigate the regulation of cytokine production in response to physiological signals in the absence of contaminating cells. The DC clones exhibited the phenotypical and functional features of DC precursors and could phagocytose, albeit at a low rate, whole bacteria. Heat-inactivated bacteria and bacterial cell wall products were tested for cytokine induction. Lipopolysaccharide, lipoteichoic acid, and gram-negative bacteria were potent inducers of tumor necrosis factor alpha and interleukin 6 release, whereas gram-positive bacteria were less efficient. The results suggest that microbial infections can directly promote cytokine DC release of relevant inflammatory responses as well as in the autocrine activation of DC.

Animals↗

Retroviral immortalization of phagocytic and dendritic cell clones as a tool to investigate functional heterogeneity.

We have developed a method to generate immortalized phagocytic and dendritic cell clones from various mouse tissues such as spleen, thymus, brain and bone marrow. The clones were phenotypically characterized and shown to retain the ability to respond to immune or inflammatory signals, e.g., IFN-gamma. Functional cytokine activity and nitric oxide production were maintained in activated macrophages, microglial and dendritic cell clones. Immune functions, such as antigen presentation was exhibited by all clones whereas tissue-specific properties such as the ability to respond to corticotropin-releasing hormone and produce beta-endorphin was shown in microglial cell clones but not in macrophage cell clones, indicating that heterogeneity of cells of the mononuclear-phagocytic lineage can be maintained in vitro after the immortalization procedure. Moreover, the continuous proliferation of the clones could be inhibited by various stimuli and further differentiation of the cells could be achieved in vitro.

Animals↗

[Clinical significance of fluoroscopic patterns specific for the mitotic spindle in patients with rheumatic diseases].

OBJECTIVE: To determine the clinical significance of anti-NuMA and anti-HsEg5 antibodies in a group of patients affected with rheumatic diseases. MATERIALS AND METHODS: Indirect immunofluorescence on HEp-2000 cells at serum dilution of 1:40 was used to examine 26 sera which had previously showed a "mitotic spindle" fluoroscopic pattern type during laboratory routine. RESULTS: 21 sera (80,7%) were identified with NuMA and 5 (19,3%) with HsEg5 patterns alone or associated with other ANA patterns. However only patients with isolated positivity and that is 15 with NuMA and 4 with HsEg5 stainings were included in this study. Of the NuMA positive patients 5 were affected with arthropathies associated to different forms of thyroiditis, 2 with seronegative arthritis, 2 with antiphospholipid syndrome, 1 with systemic lupus erythematosus (SLE), 1 with rheumatoid arthritis, 1 with sicca syndrome, 1 with undifferentiated connective tissue disease, 1 with Mycoplasma pneumoniae infection and 1 with retinal thrombosis. Of the HsEg5 positive patients 3 were affected with SLE and 1 with seronegative arthritis. CONCLUSIONS: NuMA does not prevail in any defined rheumatic disease, while HsEg5 staining were more frequent (75%) in patients affected with SLE all of whom showing high antibody titres.

Adenocarcinoma↗