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Biomedical subjects

A Franchini

Publications and source records attributed to A Franchini.

At least 55 records · Page 3Linked to original sources

Presence of immunoreactive corticotropin-releasing hormone and cortisol molecules in invertebrate haemocytes and lower and higher vertebrate thymus.

Corticotropin-releasing hormone- and cortisol-like molecules are present in the haemocytes of different molluscan species and in the epithelial cells, interdigitating cells and macrophages - but not in the lymphocytes - of fish, frog, chicken and rat thymus. Taking into account the fact that other pro-opiomelanocortin-derived peptides, such as adrenocorticotropin hormone, are present in the haemocytes and thymus of the same species, these results complete the list of stress mediators present in molluscan haemocytes and further support the hypothesis that, although the prototype stress response we have demonstrated in invertebrates is concentrated in a single cell, i.e. the haemocyte, it is similar to the response seen in vertebrates. Moreover, the data presented here are compatible with the hypothesis that an evolutionary, conserved stress response can occur locally with a single organ, e.g. the thymus, in which all the main mediators of this biological response, such as corticotropin-releasing hormone, adrenocorticotropin hormone and glucocorticoids, are present. The implications of these findings for the physiology of thymus and stress response may be far reaching.

Animals↗

Secretion of apoB- and apoA-I-containing lipoproteins by chick kidney.

Previous studies showed that chick kidney is a site of synthesis of apolipoprotein (apo) B(B-100) and A-I. Aims of the present study were: a) to compare apoB and apoA-I production in chick kidney and liver; b) to investigate whether kidney apolipoproteins were secreted as constituents of lipoproteins; and c) to define the cellular sites of renal apolipoprotein synthesis. Kidney and liver slices taken from the same animals were incubated with 35S-labeled amino acids and radioactive apoB and apoA-I were immunoprecipitated from cell homogenate and incubation medium. The percentage of total protein radioactivity incorporated into cell plus medium apoB and apoA-I was 0.23+/-0.08 and 0.19+/-0.11 in kidney and 0.38+/-0.05 and 0.38+/-0.07 in liver, respectively (P < 0.05 kidney vs. liver). 35S-labeled medium lipoproteins were separated by density gradient ultracentrifugation and three major classes corresponding to VLDL + IDL, LDL, and HDL were identified. Most of the apoB secreted by the liver was found in VLDL, IDL, and LDL whereas kidney apoB was found in VLDL, LDL and "light" HDL (d 1.070-1.130 g/ml). In both hepatic and renal lipoproteins apoA-I was found not only in HDL but also in the other lipoproteins. Immunohistochemical analysis of kidney sections showed that apoB and apoA-I were present almost exclusively in the epithelial cells of proximal and distal convoluted tubules. Thus apoB and apoA-I synthesized by the epithelial cells of the proximal and distal convoluted tubules of chick kidneys are secreted as constituents of lipoprotein particles floating within the density range of plasma lipoproteins. These observations suggest that in the chick, the kidneys may contribute to the plasma lipoprotein pool.

Amino Acids↗

Pro-opiomelanocortin-derived peptides, cytokines, and nitric oxide in immune responses and stress: an evolutionary approach.

In vertebrates, including man, the study of stress has contributed substantially to unravelling the complex relationship between immune-neuroendocrine interactions and the systems involved. On the basis of data on the presence and distribution of the main actors (POMC products, cytokines, biogenic amines, and steroid hormones) in different species and taxa from invertebrates to vertebrates, we argue that these responses have been deeply connected and interrelated since the beginning of life. Moreover, the study of nitric oxide suggests that the inflammatory reaction is located precisely between the immune and stress responses, sharing the same fundamental evolutionary roots. The major argument in favor of this hypothesis is that the immune, stress, and inflammation responses appear to be mediated by a common pool of molecules that have been conserved throughout evolution and that from a network of adaptive mechanisms. One cell type, the macrophage, appears to emerge as that most capable of supporting this network critical for survival; it was probably a major target of selective pressure. All these data fit the unitarian hypothesis we propose, by which evolution favors what has been conserved, rather than what has changed, as far as both molecules and functions are concerned.

Animals↗

Evolution of neuroendocrine thymus: studies on POMC-derived peptides, cytokines and apoptosis in lower and higher vertebrates.

In previous papers, we showed that neuroendocrine cells reactive to anti-POMC-derived peptides and cytokines are present in the thymus of a fish and an anuran amphibian. Here we report that this phenomenon is general, as neuroendocrine cells positive to anti-POMC-derived peptides (ACTH, beta-endorphin, alpha-MSH) and cytokines (IL-1 alpha, IL-2, IL-6, TNF-alpha) are also present in the thymus of chicken and rat. However, the number and the intrathymic localization and distribution of these cells varies in the different species examined. An analysis of apoptotic cells or cells involved in apoptosis, such as interdigitating cells and macrophages, in fish, frog, chicken and rat thymus, using an immunocytochemical method and anti-DNA mAb conjugated with peroxidase (anti-DNA-POD), showed that cells positive to anti-DNA-POD mAb are present in the same thymic areas in which POMC-derived peptides and cytokines were found. In conclusion, these data on apoptotic cells in the thymus of lower and higher vertebrates are compatible with the hypothesis that neuroendocrine cells might play a role in the selection and apoptosis of thymic lymphocytes, a phenomenon which could vary slightly in different species and taxa.

Animals↗

Immunocytochemical evidence of PDGF- and TGF-beta-like molecules in invertebrate and vertebrate immunocytes: an evolutionary approach.

Immunoreactive platelet-derived growth factor-AB and transforming growth factor-beta 1 were demonstrated in invertebrate and vertebrate immunocytes by an immunocytochemical procedure. These factors are only present in phagocytic cells among invertebrate immunocytes, whereas in vertebrate immunocytes they are found in monocytes, granulocytes, lymphocytes, thrombocytes and platelets. These results, in agreement with previous reports, represent further evidence in favour of the hypothesis that Nature has followed a conservative strategy in using a common pool of signal molecules that have been highly conserved throughout evolution.

Animals↗

Presence of casein immunoreactive epitopes in molluscs, fish and frog.

The presence of a group of peptides derived from milk proteins (caseins) was examined by immunocytochemistry in various tissues from invertebrates and lower vertebrates. Phagocytic hemocytes from different species of molluscs, and cells located in the intestine wall or in related glands of invertebrates and lower vertebrates showed immunoreactivity to antibodies to whole casein and related fragments. Several functional tests (cell migration, inhibition test, phagocytosis) using these peptides were performed on the mollusc hemocytes. Only ovine caseinoglycopeptide was able to increase the phagocytic activity of the hemocytes towards bacteria.

Animals↗

Induction of ACTH- and TNF-alpha-like molecules in the hemocytes of Calliphora vomitoria (Insecta, Diptera).

Three basic cell types are described in the hemolymph of newly enclosed adult Calliphora vomitoria: prohemocytes, plasmatocytes, and granular cells. In addition, anucleate cellular fragments with some inclusions are observed. Cell division is found only in the prohemocytes. Plasmatocytes and granular cells are capable of in vitro bacterial phagocytosis and take part in capsule formation. Adrenocorticotropin hormone (ACTH)-like molecules are found in both cell types. The staining of the plasmatocytes is related to the functional activation of the cells. Indeed, positive staining is only observed during capsule formation, suggesting an induction of ACTH expression. The behaviour of tumor necrosis factor (TNF)-alpha-like molecules is similar. In conclusion, these data provide further support for the close, evolutionary relationship between the immune and the neuroendocrine systems.

Adrenocorticotropic Hormone↗

Antagonizing effect of morphine on the mobility and phagocytic activity of invertebrate immunocytes.

In the present study we have demonstrated that lipopolysaccharide (LPS) acts as an activator in the immunocytes of molluscs Planorbarius corneus, Mytilus edulis, and the insect Leucophaea maderae. This stimulatory effect, demonstrated by cellular conformational changes, is concentration- and time-dependent, and is antagonized by morphine. The inhibitory effect of morphine can be counteracted by naloxone. Morphine inhibitory action on immunocyte activity is also demonstrated by a decrease in the phagocytic activity. These data suggest that the downregulation of morphine is not limited to vertebrates but is also present in invertebrates.

Animals↗

Nitric oxide: an ancestral immunocyte effector molecule.

The presence and the role of nitric oxide synthase (NOS) were investigated in the molluscan hemocytes by immunocytochemical, biochemical and functional approaches. Using an anti-NOS polyclonal antibody, immunoreactivity was observed in the hemocytes, and this reactivity increased after stimulation of the animals with Escherichia coli, indicating that this enzyme is inducible. The NOS inducibility was also histochemically demonstrated by detection of NADPH-diaphorase activity. Biochemical studies show that the enzyme is 70% cytoplasmatic and 30% membrane bound and that the inducible form is mainly cytoplasmatic. The nitrite + nitrate and citrulline formation, the inhibition by N omega-nitro-L-arginine, the Km value for arginine, the calcium and co-enzyme dependence show that the molluscan NOS shares the same properties as the NOS isoenzymes so far studied. However, it cannot be identified with any of these enzymes. It appears to be in some way similar to an inducible form of human hepatocyte NOS. Also cytokines are able to induce NOS. In vitro studies have shown that hemocytes produce nitric oxide (NO), a bactericide substance, and that there is a relationship between the NO system and phagocytosis. The presence of NO in the invertebrate hemocyte demonstrates that critical molecules have been conserved over the course of evolution.

Animals↗

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↗

Vitamin E in viral inactivated vaccines.

This research aimed at verifying whether vitamin E added to inactivated and emulsified vaccines enhances the immune response to viral antigens in chicken. Three hundred and twenty broilers (males and females) and 16 types of vaccines, varying in viral antigen [Newcastle disease virus, egg drop syndrome 1976 virus (EDS76V), and infectious bursal disease virus] and vitamin E amount (replacing 10, 20, and 30% of mineral oil) were used. Results show that vaccines with vitamin E, especially when it replaces 20 or 30% of mineral oil, induces a more rapid and higher antibody response than control vaccines. An adjuvant effect of vitamin E was also present in viral vaccine lacking bacterial antigens. Apart from vitamin E content, the Newcastle disease virus and infectious bursal disease virus monovalent vaccines induced higher titers of specific circulating antibodies in birds than did trivalent vaccines.

Animals↗

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↗

Immune and neuroendocrine responses in molluscs: the role of cytokines.

In this paper, we overview the data obtained on the presence of cytokine-like molecules in molluscam hemocytes and on the relationships between mammalian cytokines and molluscan immune-neuroendocrine responses. Only the hemocytes with phagocytic activity show immunoreactivity to the different cytokines tested (IL-1 alpha, IL-1 beta, IL-2, IL-6 and TNF-alpha). Mammalian cytokines are able to affect cell motility, bacterial phagocytosis, induction of nitric oxide synthase and the release of biogenic amines by hemocytes. Moreover, we provide evidence suggesting that the cytokines tested can bind to and compete with CRF for the same membrane hemocyte receptor. Our findings indicate that these molecules are ancestral and have maintained their pleiotropicity, functional redundancy and receptor promiscuity.

Animals↗

Cytokines and invertebrate immune responses.

A profound interrelationship between cytokines and invertebrate (molluscs) immune responses has been reported. Different cytokines (IL-1 alpha, IL-2 and TNF-alpha) significantly stimulate molluscan hemocyte motility, increasing phagocytic activity and provoking the induction of nitric oxide synthase. As far as cell motility is concerned, the response to different cytokines varied between species. These and other recently reported findings (Ottaviani et al (1994) FEBS Lett 351, 19-21; Ottaviani et al (1995) Biochem Biophys Res Commun 207, 288-292) suggest that cytokines are important, ancestral, and functionally conserved molecules, which have also maintained their pleiotropicity, redundancy in the mode of action, and high promiscuity of their receptors during evolution.

Animals↗

Relationship between corticotropin-releasing factor and interleukin-2: evolutionary evidence.

The addition of corticotropin-releasing factor (CRF) to molluscan hemocytes induces the release of biogenic amines (norepinephrine, epinephrine, dopamine), a phenomenon we have considered as an ancestral type of stress response [(1992) Gen. Comp. Endocrinol. 87, 354-360]. A similar but less significant response was observed following the addition of interleukin-2 (IL-2). Pre-incubation of hemocytes with IL-2 or anti-IL-2 monoclonal antibody significantly reduced or completely eliminated the CRF-induced release of biogenic amines. Further direct evidence of competition between CRF and IL-2 was revealed by immunocytochemical and cytofluorimetric analysis. The data are compatible with the presence of a unique (ancestral?) receptor on molluscan hemocytes, capable of binding both CRF and IL-2, two key molecules of the neuroendocrine and immune system, respectively.

Animals↗

D-ribose and deoxy-D-ribose induce apoptosis in human quiescent peripheral blood mononuclear cells.

In previous papers we reported that D(-)-ribose and 2-deoxy-D-ribose, which rank at the top among reducing sugars, kill a variety of human and animal cells and cell lines. Here we demonstrate that these two sugars induce apoptosis in human quiescent peripheral blood mononuclear cells which are relatively insensitive to apoptosis. Apoptosis was assessed by morphological changes, DNA fragmentation by agarose gel electrophoresis and the appearance of an hypodiploid peak by flow cytometry. 2-deoxy-D-ribose was more potent than D(-)-ribose and apoptosis was evident from 48 hours of culture onwards. 2-deoxy-D-ribose-induced apoptosis was inhibited by N-acetyl-L-cysteine, suggesting that glutathione metabolism and/or oxidative stress are involved in this type of apoptosis. Thus, D(-)-ribose and 2-deoxy-D-ribose can be useful tools to study the cellular and molecular events of apoptosis in human quiescent lymphocytes.

Acetylcysteine↗