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Biomedical subjects

C Franceschi

Publications and source records attributed to C Franceschi.

At least 199 records · Page 11Linked to original sources
PubMed1995

Cytokines and evolution: in vitro effects of IL-1 alpha, IL-1 beta, TNF-alpha and TNF-beta on an ancestral type of stress response.

Invertebrate hemocytes are immune-neuroendocrine cells which contain a variety of cytokines [Ottaviani et al. (1993) Biochem. Biophys. Res. Commun. 195, 984-988] and release biogenic amines when added to corticotropin-releasing factor (CRF), a phenomenon we have described as an evolutionary proto-type stress response [Ottaviani et al. (1991) Proc. R. Soc. Lond. B 245, 215-218]. Here we show in two molluscs, Planorbarius corneus and Viviparus ater, that this response is significantly reduced when hemocytes are pre-incubated with IL-1 alpha, IL-1 beta, TNF-alpha and TNF-beta before the addition of CRF. These results confirm and extend the hypothesis that a deep evolutionary relationship exists between cytokines and stress response. Moreover, these data offer an evolutionary basis for understanding the promiscuity of cytokine receptors.

Animals↗
PubMed1995

Invertebrate and vertebrate immune cells express pro-opiomelanocortin (POMC) mRNA.

We show here that hemocytes and leukocytes with phagocytic activity from both invertebrates (Planorbarius corneus, Viviparus ater) and vertebrates (Carassius auratus, Rana esculenta) express pro-opiomelanocortin (POMC) mRNA, as assessed by in situ hybridization with a digoxigenin-labeled human DNA probe. These data are in accord with previous observations from our laboratories on the presence in these cells of POMC-derived peptides and strongly suggest that these molecules--highly conserved throughout evolution--play an important role in cell locomotion and phagocytosis. POMC mRNA was also detected in lymphocytes of R. esculenta, but not of C. auratus, suggesting that from anuran amphibians onwards lymphocytes also express this gene. This phenomenon could be related to the appearance of more than one immunoglobulin isotype in anurans.

Animals↗
PubMed1995

Autogeneic but not allogeneic earthworm effector coelomocytes kill the mammalian tumor cell target K562.

Earthworm coelomocytes have been used as effector cells against the human tumor target, K562. To first assess the viability of effectors, incorporation of [3H]-thymidine was tested and was higher in autogeneic (A<==A, self) than in allogeneic (A<==>B, nonself) coelomocytes. A<==>A showed significantly greater numbers in S, G2, or M phases than A<==>B coelomocytes. When A<==>A or A<==>B were cultured, no significant cell killing occurred in either, as measured in a 4-hr 51Cr release assay. A<==>A but not A<==>B killed K562 target cells. Cytotoxicity was dependent upon membrane binding between small, electron-dense coelomocytes and targets; it was enhanced by adding PHA. The heat labile supernatant from A<==>A but not from A<==>B killed K562 targets after cultivation for 10 min at 22 degrees C, but not immediately after washing. Recognition of, binding to, and killing of foreign cells in a natural killer cell-like reaction may reflect natural immunity in earthworms.

Animals↗
PubMed1995

Protective effect of N-acetylcysteine in tumor necrosis factor-alpha-induced apoptosis in U937 cells: the role of mitochondria.

The existence of two different pathways for cell death has been postulated. In addition to the passive and traumatic process leading to necrosis, an active program characterized by organelle integrity and called apoptosis has been described. A positive correlation between the apoptotic cell death process and oxidative imbalance has been demonstrated. In fact, the antioxidant N-acetylcysteine (NAC) seems to be capable of impairing the apoptotic program, replenishing intracellular reduced glutathione content in cells exposed to tumor necrosis factor-alpha (TNF) as apoptotic inducer. Moreover, protein synthesis inhibitors such as cycloheximide (CHX) can facilitate apoptotic triggering by TNF, and mitochondrial function was suggested to be essential in the TNF-mediated apoptotic process. With this in mind, a specific analysis using the JC-1 probe, a fluorescent dye which is capable of indicating mitochondrial membrane potential (delta psi m) changes, was carried out. Our results show that TNF exposure is capable of altering the mitochondria and that NAC protection from CHX + TNF-induced apoptosis could be due to a direct effect of the drug on mitochondrial integrity and function.

Acetylcysteine↗
PubMed1995

The immunology of exceptional individuals: the lesson of centenarians.

Centenarians are the best example of successful ageing, since they have escaped the major age-associated diseases, and most are in good mental and physical condition. Here, Claudio Franceschi and colleagues discuss how the study of their immune systems reveals that several immune parameters are well conserved, suggesting that a complex remodelling of most immune parameters occurs with age, rather than a unidirectional deterioration.

Aged↗
PubMed1995

Presence of immunoreactive pro-opiomelanocortin-derived peptides and cytokines in the thymus of an anuran amphibian (Rana esculenta).

Pro-opiomelanocortin (POMC)-derived peptide [adrenocorticotropic hormone (ACTH), beta-endorphin, alpha-melanocyte-stimulating hormone (MSH)]- and cytokine (IL-1 alpha, IL-1 beta, IL-2, IL-6, TNF-alpha)-like molecules were demonstrated in PAS positive epithelial cells of the thymus of the anuran amphibian Rana esculenta by an immunocytochemical procedure. Three groups of PAS positive epithelial cells were identified in subcapsular cortex, inner cortex and medulla, respectively. The cells containing ACTH-, alpha-MSH- and cytokine-like molecules were distributed in the cortex and those containing beta-endorphin-like molecules in the medulla and inner cortex. Thymic lymphocytes were always negative for POMC-derived peptides and cytokines. These results suggest that the neuroendocrine function of the thymus can be traced back to lower vertebrates.

Animals↗
PubMed1995

Human natural killer cytotoxic activity is not affected by in vitro exposure to 50-Hz sinusoidal magnetic fields.

Epidemiological studies have suggested, but not demonstrated, a role of exposure to 50/60-Hz magnetic fields in increasing cancer risk in man (workers and the general population). A possible target of magnetic fields is the immune system. In particular, it is known that an important defence against cancer is represented by natural killer (NK) cells capable of killing cancer cell targets. To test this hypothesis, human NK cells, stimulated or not with phytohaemagglutinin or interleukin 2, were exposed to 50-Hz sinusoidal magnetic fields before or during the cytotoxicity test, and then mixed with a variety of target cancer cell lines (Daudi, Raji, U937, H14, IGROV, SW626, K562, HL60). The experiments were performed in two laboratories (Rome and Modena) by means of two different exposure systems. The results of both laboratories suggest that 50-Hz sinusoidal magnetic fields with flux densities up to 10 mT do not affect the cytotoxic activity of human NK cells.

Adult↗
PubMed1995

Massive activation of immune cells with an intact T cell repertoire in acute human immunodeficiency virus syndrome.

In 8 patients with symptomatic, acute primary infection with human immunodeficiency virus (HIV), a dramatic and persistent decrease in CD4+ lymphocytes was seen, accompanied by a marked increase in activated/memory CD8+ T cells (CD38+, CD45R0+, HLA-DR+, with high amounts of cell adhesion molecules), which represented most circulating lymphocytes, but no gross alterations in V beta T cell repertoire. Extremely high plasma levels of proinflammatory cytokines were observed. Three patients were followed for 2-3 years: The number of CD4+ cells, extremely low at first, increased significantly in a few months but decreased rapidly after a short stable period. Cytotoxic T lymphocytes bearing markers of immunologic activation/memory could play an important role in the earliest phases of the disease. It remains to be established how such a dramatic onset could determine the rapid progression of the infection that seems characteristic of patients with acute HIV syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Thyroid autoimmunity and ageing.

Ageing is associated with the appearance of several serum autoantibodies, including thyroid autoantibodies. The biological and clinical significance of this phenomenon is still unknown, since, with the exception of primary myxedema, the prevalence of clinically overt thyroid autoimmune diseases is not increased in the elderly. The peculiar link between autoimmune thyroid failure and ageing is also underscored by the high prevalence of subclinical hypothyroidism in elderly subjects with positive serum thyroid autoantibodies, and could be the consequence of preferential age-dependent expression of destructive effector mechanisms and/or increased target gland susceptibility. Thyroid autoimmunity and subclinical hypothyroidism have also been implicated in the pathogenesis of other age-associated disorders, in particular coronary heart disease. Interestingly, recent data from our laboratories showed that thyroid autoantibodies are rare in healthy centenarians and in other highly selected aged populations, while they are frequently observed in unselected or hospitalized elderly. Taken together, these data suggest that thyroid autoimmune phenomena are not the consequence of the ageing process itself, but rather might be related to age-associated disease.

Aging↗
PubMed1995

Involvement of ornithine decarboxylase and polyamines in glucocorticoid-induced apoptosis of rat thymocytes.

Ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine metabolism, has been shown to be required for entry into and progression through the cell cycle. However, the role of ODC and polyamines in apoptosis remains to be determined. We have examined ODC expression and polyamine levels in thymocytes activated to undergo apoptosis by dexamethasone treatment. We have demonstrated a rapid and reversible induction of ODC (mRNA and activity), as previously reported for the mRNA expression of other "early" genes, c-fos, c-jun, and c-myc, in the same experimental model. Surprisingly, polyamine levels diminished progressively starting at 2-4 h after dexamethasone treatment, and spermine was depleted at 8-12 h. This seemed to be relevant since increasing the intracellular polyamine levels by exogenous spermine administration prevented the DNA "laddering" (2-4 h) and the DNA loss from the nucleus (8-18 h) due to dexamethasone treatment. Moreover, the activities of spermidine/spermine N1-acetyltransferase, which controls the cytosolic polyamine interconversion pathway, and of spermidine N8-acetyltransferase, which regulates the nuclear pool and functions of polyamines, were measured in apoptotic cells. Spermidine/spermine N1-acetyltransferase activity progressively increased and might be responsible for spermidine and spermine excretion as acetyl derivatives. In contrast, spermidine N8-acetyltransferase activity remained unchanged. A completely different scenario was observed in proliferating concanavalin A-treated thymocytes, studied for comparison. In this case, polyamine levels increased, remaining at high values until 12 h. This is likely a consequence of the rapid and prolonged induction of ODC (mRNA and activity), accompanied by that of spermidine/spermine N1-acetyltransferase (mRNA and activity).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyltransferases↗
PubMed1995

Evidence for dissimilar mechanisms of enhancement of inorganic and organic hydroperoxide cytotoxicity by L-histidine.

L-Histidine markedly increases inorganic and organic hydroperoxide-induced cytotoxicity and DNA single-strand breaks (SSBs) in Chinese hamster ovary cells. These effects were prevented by the iron chelator o-phenanthroline and were insensitive to the antioxidant N,N'-diphenyl-1,4-phenylenediamine. An excess of L-glutamine, a competitive inhibitor of L-histidine uptake, prevented the L-histidine-mediated enhancement of cytotoxicity induced by both inorganic and organic peroxides. L-Glutamine did not affect the level of DNA SSBs produced by H2O2/L-histidine, although it abolished the enhancement of SSB formation triggered by L-histidine in cells exposed to the organic peroxides. DNA SSBs generated by the organic hydroperoxides either alone or associated with L-histidine were removed with superimposable kinetics, whereas those produced by H2O2 in the presence of the amino acid were repaired more slowly than SSBs produced by the oxidant alone. DNA double-strand breaks, which are considered to be highly cytotoxic, were detected only in cells treated with H2O2 and L-histidine. Finally, L-histidine was shown to markedly increase the extent of mitochondrial damage produced by organic but not by inorganic hydroperoxides.

Animals↗
PubMed1995

Evidence for the presence of immunoreactive POMC-derived peptides and cytokines in the thymus of the goldfish (Carassius c. auratus).

The presence of immunoreactive pro-opiomelanocortin (POMC)-derived peptides (adrenocorticotropin hormone, beta-endorphin, alpha-melanocyte-stimulating hormone) and of cytokine-like molecules [interleukin (I)-1 alpha, IL-1 beta, IL-2, Il-6, tumour necrosis factor-alpha] was demonstrated in periodic acid-Schiff-positive epithelial cells in the thymus of the goldfish (Carassius c. auratus) using immunocytochemical procedures. POMC-derived peptide- and cytokine-like molecules were localized in the same cell type. Lymphocytes were negative for all the above mentioned molecules. Despite the smaller number of cells positive for neuropeptide- and cytokine-like molecules, our findings suggest that immune-neuroendocrine interactions are likely to occur in the thymus of goldfish.

Animals↗
PubMed1995

Adherence of human monocytes to haemodialysis membranes: LFA 1 (CD11a/CD18) CR1 (CD35) and CR3 (CD11b/CD18) triggering promotes the biosynthesis of platelet-activating factor and adherence.

BACKGROUND: Platelet-activating factor is a mediator of inflammation involved in the blood-membrane interaction. We report that selective stimulation of complement receptors (CR1 and CR3) triggers PAF synthesis and monocyte adherence to complement-activating membranes. METHODS: The synthesis of PAF was studied after stimulation of normal human adherent monocytes with F(ab)2 and Fab fragments of monoclonal antibodies specific to CR1 and CR3. CD11a, CD11b, CD18, and CD35 was studied by flow cytometry on neutrophils and monocytes. The molecular species of PAF from stimulated monocytes were identified by reverse-phase high-performance liquid chromatography coupled with mass spectrometry. RESULTS: Anti-CR1 and anti-CR3 monoclonal antibodies induced a dose-dependent C-16 but not C-18 PAF production. The latter occurred also with monovalent Fab fragments of both anti-CR1 and anti-CR3 monoclonal antibodies, that were not internalized as seen by immunofluorescence. Adherence of monocytes to Cuprophan membranes was markedly higher (P < 0.01) in membranes pretreated with fresh than with heat-inactivated normal plasma. However, the high adherence to fresh plasma-treated membranes was completely abrogated by coincubating the cells with Web 2170, a specific PAF receptor antagonist. This was not due to downregulation of adhesion molecules expression on leukocytes. CONCLUSIONS: These studies implicate a crucial role of PAF in blood interaction with haemodialysis membranes that fix complement activated products.

Antibodies, Monoclonal↗