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F Chiappelli

Publications and source records attributed to F Chiappelli.

At least 37 records · Page 2Linked to original sources
PubMed1995

Fetal alcohol and thymocyte phenotypes in offspring: response to food deprivation.

Restriction of food availability is a reliable stimulus that leads to significant hypothalamo-pituitary-adrenal (HPA) activation to which rats do not habituate. Based on our previous data that indicated that the HPA response to some, but not all, stressful stimuli is significantly greater in adult offspring of Sprague-Dawley dams exposed to 35% alcohol during the last 2 weeks of gestation than that of control rats and on the mounting neuroendocrine-immune literature that describes the role of pituitary-adrenal products in modulating cellular immunity, we hypothesized that the outcomes of food restriction would be significantly more marked in fetal alcohol-exposed (FAE) offspring, compared with control rats. Data we report herein show that--whereas food restriction at 30-35 days of age produced significant changes in body weight, thymus weight-to-body weight ratio, adrenal weight-to-body weight ratio, plasma corticosterone levels, and in thymocyte number, as well as in the percentage and absolute number of CD4+ and CD8+ thymocytes that express CD45RC-FAE and control rats were equally affected. We conclude that food restriction is another example of a stressful stimulus that fails to distinguish satisfactorily between FAE and control rats of prepubertal age.

Animals↗
PubMed1995

Immunotoxicity of cocaethylene.

This report describes the response of normal human T cells to stimulation in vitro in the presence of nano-micromolar concentrations of cocaethylene. Thymidine incorporation by concanavalin A-stimulated peripheral blood mononuclear cells was generally blunted by cocaethylene, albeit to different degrees depending upon the donor tested. The formation of concanavalin A-induced blast cells was decreased by increasing concentrations of cocaethylene. The production of interleukin-2 was also blunted in a dose-dependent fashion by cocaethylene, and this outcome was more consistently observed in stimulated peripheral blood mononuclear cells, compared to unseparated whole blood preparations. An inverse dose dependence was obtained in relation to the response of blast cells to recombinant human interleukin-2 in the presence of cocaethylene. These lines of evidence, taken together with our preliminary studies aimed at testing the effect of cocaethylene on the expression of certain membrane markers of activation (i.e., interleukin-2 receptor, transferrin receptor, serine aminopeptidase IV) and the expression of the proliferating cell nuclear antigen (cyclin PCNA), suggest that cocaethylene modulates relatively early events following T cell stimulation probably related to the interleukin-2 system.

Cells, Cultured↗
PubMed1995

Immune surveillance of the oral cavity and lymphocyte migration: relevance for alcohol abusers.

The health of the oral cavity is threatened by a variety of microorganisms. Impaired immune surveillance of the oral environment contributes to the development of infectious processes and tumors of the mouth. Elucidation of the physiological mechanisms that determine and control oral immune surveillance is crucial to an understanding of these oral diseases. The ability of lymphocytes to migrate is critical for successful immune surveillance. the cardinal facets of lymphocyte migration are reviewed here in the context of the oral cavity. One mechanism by which alcohol acts as an important cofactor in the onset and development of oral diseases is hypothesized to be through impaired lymphocyte migration to and from peri-oral lymphoid tissue.

Alcoholism↗
PubMed1994

Steroid receptor-mediated modulation of CD4+CD62L+ cell homing. Implications for drug abusers.

Naive human T cells home to peripheral lymph nodes via the leukocyte endothelial cell adhesion molecule-1 (LECAM-1, l-selectin, CD62L, Leu8 antigen) they express. We enriched populations of CD4+CD62L+ cells (attachment of Leu8+ T cells to flasks coated with anti-mouse IgG (AIS); Leu8+ T cells, 82.3% pure (+/- 2.3%), enriched for CD4+ cells by incubation over flasks coated with anti-CD4 antibody--this 3-4-day procedure yields an 88 +/- 1.4% recovery. Cells were treated with dexamethasone in vitro for 24-48 h, and monitored by flow cytometry. We found severe toxicity by this steroid at high concentration (10(-6) M: 35% decrease in CD62L+ T cells, 22% drop specifically in CD4+CD62L+ cells), suggesting the onset of receptor-mediated apoptotic events. The toxicity was dose dependent (5% and 7% drop in CD62L+ T and CD4+CD62L+ cells, respectively, at 10(-9) M, the concentration found in plasma 10 h following the administration of 1 mg dexamethasone). One mg of dexamethasone given to normal subjects leads to a 15-20% decrease in circulating CD4+CD62L+ cells at 10 h. This tends to be correlated with a drop in the number of glucocorticoid cytosolic receptors. Thus, steroids seem to modulate CD4+CD62L+ cell homing by means of receptor-mediated mechanisms.

Adult↗
PubMed1994

Mitochondrial modifications during rat thymocyte apoptosis: a study at the single cell level.

Apoptosis is an active type of cell death, occurring under several physiological and pathological conditions. The role of cellular organelles such as mitochondria in this process is still an open question. We recently described a new method to measure mitochondrial membrane potential in intact cells using flow cytometry. Using this method we studied alterations of mitochondrial membrane potential in a classical model of apoptosis, i.e., dexamethasone-treated rat thymocytes. Moreover, apoptosis induced by heat shock was also studied in the same cells. Mitochondria are functionally intact during the early phases of apoptosis, when DNA fragmentation occurs, whereas early alteration in their potential and mass takes place after DNA damage. According to flow-cytometric analysis, the presence of a hypodiploid peak, an index of nuclear DNA loss, predates depolarization of mitochondrial membrane and decrease of mitochondrial mass. Loss of plasma membrane integrity, which indicates cell death and is revealed by the permeability to propidium iodide, eventually follows. All these phenomena are more evident in dexamethasone-treated cells than in heat-shocked cells. Thus, in these types of apoptosis the involvement of mitochondria is apparently not a primary event.

Animals↗
PubMed1993

Fetal alcohol exposure attenuates lipopolysaccharide-induced fever in rats.

Exposure to alcohol in utero can lead to long-lasting impairments of immune functions and to decreased resistance to infectious agents. We studied the effects of fetal alcohol exposure (FAE) in rats on the core body temperature response to an exogenous challenge of the immune system with lipopolysaccharide (LPS). We report that FAE rats show markedly decreased LPS-induced fever [i.e., they require a higher dose than control rats to show any LPS-induced hyperthermia (50 micrograms/kg vs. 10 micrograms/kg)], and even with the higher LPS dose they manifest a weaker hyperthermia, which declines faster than in control animals. These results suggest that FAE produces an impairment in the release of endogenous pyrogens and/or in the neural substrate for body temperature regulation. This impairment may account for at least some of the decreased resistance to infections observed in FAE animals and humans.

Animals↗
PubMed1993

Actions of alcohol on immunity and neoplasia in fetal alcohol exposed and adult rats.

Alterations of immune function can result not only from alcohol consumption by the adult human or animal, but also from fetal alcohol exposure (FAE). We have demonstrated long-lasting effects of FAE on T cell function and effects of adult ethanol (EtOH) consumption on tumorigenesis. Here, we present recent data that demonstrate that 1) FAE alters the biphasic pattern of thymocyte activation during peripubertal development probably due to effects other than the CD3 pathway; and 2) the long-lasting impaired proliferative response of splenocytes from FAE rats is not due to loss of their ability to express interleukin-2 receptors (IL2R), thus reflecting interference with events following the IL2-IL2R interaction. We also provide direct evidence that acute in vivo administration of EtOH to adult Fisher 344 rats can suppress blood natural killer (NK) cytotoxicity and that such suppression mediates the observed enhanced metastatic growth of a syngeneic mammary tumor.

Animals↗
PubMed1992

Beta-endorphin effects on membrane transduction in human lymphocytes.

The endogenous opioid beta-endorphin (beta E) enhances, decreases or has negligible effects on cytotoxic and proliferative responses of lymphocytes. In order to characterize the mechanisms by which beta E modulates lymphocyte functions, we have examined the effects of beta E on certain membrane transduction events. We have shown that beta E inhibits phosphoinositol phosphate metabolism, and that it can enhance or inhibit the phosphorylation of the gamma chain of CD3 in a dose-dependent manner. We present the hypothesis that beta E contemporaneously modulates several membrane transduction processes, some of which may be counteracting and thereby producing the observed mixed effects on many lymphocyte functional responses. The biochemical status of the donor's lymphocytes also contributes to the variability in beta E-mediated effects on CMI outcomes.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1992

Prenatal exposure to alcohol enhances thymocyte mitogenic responses postnatally.

Previous studies have shown altered cell-mediated immune responses in animals prenatally exposed to ethanol. The present study was designed to determine the ontogeny of proliferative responses of thymocytes postnatally following prenatal exposure to ethanol. Thymocytes obtained from 44-day old Sprague-Dawley male rats exposed to 5% (w/v) ethanol during the last two weeks of gestation had a significantly greater response to mitogenic stimulation by concanavalin A (Con A, 5.0 micrograms/ml) than controls. A similar trend was observed in rats at postnatal days 30 and 72, but not at day 16. Con A-conditioned thymoblasts from day-44 fetal alcohol-exposed animals were less responsive to further activation by a crude Con A supernatant than controls, but this response normalized by day 72. These findings reveal that the effects of ethanol exposure in utero in male rats include alterations in the development of thymoproliferative responses to mitogen which persist through the peripubertal period and normalize in part by young adulthood.

Animals↗
PubMed1992

Beta-endorphin blunts phosphatidylinositol formation during in vitro activation of isolated human lymphocytes: preliminary report.

We have previously described the regulatory effect of beta-endorphin on three human cytotoxic cell populations. We confirmed the variable nature of these effects on human natural killer cell (NK) activity, showed mixed effects on the generation of cytotoxic T lymphocyte (CTL) activity, and demonstrated the reproducible suppression of lymphokine-activated killer cell (LAK) activity. We and others also observed mixed effects of beta-endorphin on the proliferative response to mitogens and in mixed leukocyte reactions. In the study reported here, we test the effects of beta-endorphin on the formation of phosphatidylinositol during cell activation. 32P-radiolabeled peripheral blood mononuclear cells obtained from normal adult donors and CD2-depleted subpopulations were activated with phytohemagglutinin or in a NK, LAK, or CTL protocol in the absence or presence of recombinant beta-endorphin. The total lipidic extract was analyzed by thin-layer chromatography and autoradiography. The results of these studies indicate that beta-endorphin blunts the formation of phosphatidylinositol by about 20% in the four systems studied and in all the donors tested. This effect is dose-dependent and is blocked in part by the opioid antagonist, naltrexone, suggesting involvement of the opioid receptor.

Adolescent↗
PubMed1992

[The role of endogenous opioids in modulation of immunosuppression in fish].

We have previously shown that social confrontation between aggressive fish (e.g., Tilapia) produces a suppression of several immunological parameters--nonspecific cytotoxicity and mitogen-stimulated proliferation in pronephric lymphocytes--in the subordinate fish. By using the opioid antagonist, naltrexone, we now demonstrate indirectly that this immunosuppression is in part mediated by the endogenous opioid system. Evidence is presented that naltrexone-mediated reversal of immunosuppression may be limited to the populations of the cytotoxic and T-cell lineages. The proliferative response to lipopolysaccharide is unaffected by naltrexone. Our data also demonstrate that serum from subordinate (immunosuppressed) fish is immunosuppressive in normal fish: an effect that can be reversed by naltrexone. These results support a link between the neuroendocrine and immune systems in these animals.

Aggression↗
PubMed1991

Preferential reductions in lymphocyte sub-populations induced by monthly pulses of chlorambucil: studies in patients with chronic progressive multiple sclerosis.

Thirty-three patients with chronic progressive multiple sclerosis (MS) were assigned to intervention groups receiving monthly pulses of chlorambucil (CB) for about one year. The monthly doses ranged from 0.4 to 1.5 mg/kg. Administration of CB resulted in preferential reduction in different lymphocyte subsets which was dose- and time-dependent. The number of B-cells (CD20) decreased more rapidly than NK-cells (CD16, CD56, CD16+CD56+) or T-cell (CD3) and T-cells subsets (CD4 and CD8). At 1.2 mg/kg, CB administration resulted in a preferential drop of T-suppressor/cytotoxic cells (CD8) compared with T-helper cells (CD4), and of the less mature "virgin" CD4 cells (CD4+CD45RA+) compared with "memory" CD4 cells (CD4+CD45RA-). The expression of activation markers (transferrin receptor, CALLa, HLA-Dr and CD38[OKT10]) within CD4, CD8 or CD20 lymphocytes was not altered by CB administration. Our data, which show that CB administration results in a preferential fall in B-cell numbers, contrast with the effects of long-term administration of the related immunosuppressive drugs, azathioprine and cyclophosphamide.

Antigens, CD↗
PubMed1991

Differential effect of beta-endorphin on three human cytotoxic cell populations.

We have examined in vitro the effect of the proopiomelanocortin gene product, beta-endorphin (bE), on the cytotoxic activity of natural killer (NK) cells, lymphokine activated killer (LAK) cells and cytotoxic T-lymphocytes (CTL). Our studies show that bE reproducibly suppressed LAK cytotoxic activity in all donors tested. The effect of bE on the generation of CTL varied, and was negligible on CTL cytotoxic function. Our study also confirms the variable nature of the effects of bE on NK cytotoxicity. In all instances, the effects of bE were generally small, but could be blocked by opioid receptor antagonists, or by prior heat-inactivation of the peptide. The magnitude of the effects was greatest at low effector:target ratios in all of the three systems studied. These results support the emerging body of evidence that the neuroendocrine system may influence host defense mechanisms mediated by cytotoxic cells.

Adolescent↗
PubMed1991

Pituitary-adrenal-immune system in normal subjects and in patients with anorexia nervosa: the number of circulating helper T lymphocytes (CD4) expressing the homing receptor Leu8 is regulated in part by pituitary-adrenal products.

The association between plasma pituitary-adrenal (PA) hormones and the number of certain populations of peripheral blood lymphocytes (PBL) was examined in subjects with normal PA function and in patients with anorexia nervosa (AN). AN patients display several neuroendocrine dysfunctions, including hypercortisolemia. In the normal subjects there were positive correlations between adrenocorticotropic hormone (ACTH) and the number of PBL and helper T lymphocytes expressing the homing receptor Leu8 (CD4+Leu8+); there was a negative relationship between cortisol and these lymphocyte populations. These latter, inverse correlations did not occur in the AN patients, either while underweight or after weight recovery, with some persistence of hypercortisolemia. Administration of dexamethasone (DEX) suppressed cortisol levels and reduced, perhaps via a receptor-mediated mechanism, the number of circulating PBL and CD4+Leu8+ in the normal subjects but not in the AN patients. These results support the physiological relevance of PA-CMI interaction in subjects with normal PA function and indicate that the PA-CMI interrelationship is disrupted in AN patients with hypercortisolemia.

Adrenocorticotropic Hormone↗
PubMed1991

Fetal alcohol delays the developmental expression of myelin basic protein and transferrin in rat primary oligodendrocyte cultures.

This study has examined the development of immunoreactive myelin basic protein and transferrin in primary glial cell cultures. Cultures were initiated from control and experimental Sprague-Dawley rats 1-2 days postnatally. Experimental treatment involved exposure to 5% (w/v) ethanol in a liquid diet during the last two weeks of gestation. Prenatal alcohol administration delayed the expression of myelin basic protein and transferrin during the first three weeks postnatally. Other oligodendroglial and astroglial markers were little affected, if at all, by fetal alcohol exposure.

Animals↗
PubMed1990

Growth and development of brain of artificially reared hypoketonemic rat pups.

Three groups of rats were reared: mother-reared controls; artificially reared controls (AR-c), which were fed a milk substitute with the same composition of macro-nutrients as natural rat's milk; and an artificially reared test group (AR-h), which was fed a milk substitute identical to that fed AR-c pups except that the component of fat containing medium chain length fatty acids was omitted (medium chain triglyceride deficient) and replaced on an isocaloric basis with carbohydrate. The AR rats were fed the milk substitute from postnatal Day 5 until Day 17 by fitting them with gastric cannulas through which the milk could be infused automatically. The nutritional impact of the milk substitutes on growth and the integrity of the brain was assessed by a comparison of morphologic and biochemical markers. Pups in the AR-h group were hypoketonemic. Animals in all groups attained the same body weight by Day 17 and there was no difference in the morphologic markers among the groups with one exception: the vibrissal "barrel fields" of the somatosensory cortex of rat pups in both AR groups were reduced in size but not in number of distribution from those of the mother-reared groups. Furthermore, the brains of the rat pups in the AR groups were not different in weight, but they weighed less than brains of mother-reared controls. Our data show that although there are many similarities in the status of AR rat pups when compared with mother-reared controls, distinctive differences associated with artificial rearing are evident. We conclude that medium chain fatty acids in milk fat and the circulating ketone bodies are not mandatory substrates for growth and the development of the brain. Mechanisms must exist whereby alternative substrates are used to compensate when these metabolites are diminished in supply.

Animal Nutritional Physiological Phenomena↗