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Biomedical subjects

D Delfino

Publications and source records attributed to D Delfino.

40 records · Page 3Linked to original sources

Effect of oral administration of a variety of bacteria on depressed macrophage functions in tumour-bearing rats.

In consideration of the well documented influence of normal microbial flora on the level of activation of macrophages, we evaluated the effects of oral administration of bacteria on rats with depressed macrophage functions. An oral, killed polyvalent vaccine (Diplococcus pneumoniae types I, II and III, Streptococcus haemolyticus, Staphylococcus aureus and Haemophilus influenzae), the live lyophilized Streptococcus faecium and spores of Bacillus subtilis, respectively, were administered orally to immuno-depressed rats. Results demonstrate the restoration of phagocytosis, intracellular killing and the chemotactic activity of macrophages. These experimental observations suggest that bacterial flora associated with mucosae can influence the level of activation of peritoneal macrophages.

Administration, Oral↗

Glucocorticoid hormones in the regulation of cell death.

The immune T-cell compartment maintains the capability to respond to a wide variety of antigens (Ag). This whole process is regulated by lymphocyte apoptosis (programmed cell death, PCD) and involves the coordinated expression of a great number of genes including those coding for cytokines and their receptors, such as for example IL-2/IL-2R and the Fas/FasL systems and those coding for transcription factors, including the NF-kB complex, involved in T-cell activation and apoptosis in that they simultaneously activate cell suicide and an anti-death programme. This binary effect, PCD activation and inhibition, is due on one hand to GCH-induced activation of the caspases cascade and on the other to the induction of expression of a new gene that we have named GILZ. In fact, GILZ over-expression in transfected cells inhibits the sequential increase of NF-kB/DNA-binding activity, IL-2 production and IL-2R expression, and transcription of the Fas/FasL complex that follows TCR triggering and plays an important role in the control of T-lymphocyte apoptosis. These results indicate a new mechanism responsible for the GCH-mediated inhibition of T-cell death and activation that could contribute to anti-inflammatory and immunosuppressive efficacy.

Animals↗

Long-term cultures of mouse bone marrow cells: a model for studying the generation of natural killer cells.

We investigated the generation of natural killer (NK) cells, using a long-term bone marrow culture (LTBMC) system. Mouse bone marrow cells were cultured for 2 weeks in complete medium without growth factors to obtain an enriched population of NK precursor cells. When these cells were recultured in the presence of interleukin-2 (IL-2) and conditioned medium (CM) from LTBMC, lytic NK cells were generated within 4 days. Replacing CM with fresh medium, before adding IL-2, decreased NK cell generation markedly, suggesting that endogenous factors present in CM were necessary for IL-2 induction of NK cells. NK cell precursors were also cultured with a combination of IL-2 and interferon-gamma (IFN-gamma) or IL-2 and tumor necrosis factor-alpha (TNF-alpha), but no CM. Results show that IFN-gamma and TNF-alpha were able to substitute CM. The addition of anti-IFN-gamma or anti-TNF-alpha antibodies to LTBMC cells, cultured in the presence of IL-2 and CM, inhibited cytotoxicity induction in a dose-dependent manner. The data indicate that IFN-gamma and TNF-alpha production may be required for IL-2 induction of NK activity, and are consistent with the hypothesis that NK generation involves collaboration between IL-2 and other bone marrow microenvironmental growth factors.

Animals↗

Generation of natural killer cells from long-term cultures of mouse bone marrow.

The features of a mouse long-term bone marrow culture (LTBMC) system that produces natural killer (NK) cell activity are described. Over a 4-week period in the NK-LTBMC, cellularity dropped from approximately 2.5 x 10(7) to 8 x 10(5) cells/25-cm2 flask. About 3 x 10(5) of these cells were loosely adherent. The cultures at this time contained about one-third the spleen colony forming units, one-tenth the granulocyte macrophage colony forming units and about one-third the transplantable NK progenitor activity of fresh bone marrow (BM), and no detectable NK cell activity. In the 4-week NK-LTBMC, IL-2-responsive precursor cells appeared to be selectively maintained and gave an 8-fold higher activity after culture with human recombinant IL-2 (rIL-2) than did fresh BM. The addition of 50-5,000 IU/ml of rIL-2 resulted, after a minimal 3-day lag, in progressively increased cellularity for as long as 13 days. The percentage and staining intensity of NK-1.1+ cells increased with time after addition of rIL-2. CD3 epsilon + cells were occasionally seen and B220+ cells were present in low numbers at day 7 and slowly increased through day 13. The stroma was necessary for IL-2-dependent development of NK activity.

Animals↗