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T Marotti

Publications and source records attributed to T Marotti.

At least 37 records · Page 2Linked to original sources
PubMed1994

Modulation of lipopolysaccharide-induced production of cytokines by methionine-enkephalin.

In the present study, we have examined the effect of opioid peptide methionine enkephalin (MENK) on production of factors with interleukin-1 (IL-1) and tumor necrosis factor (TNF) activity by mouse peritoneal macrophages and assessed whether modification in the production of those cytokines could be related to alteration of phagocytosis by MENK. None of the MENK concentrations examined altered IL-1 or TNF activity alone. However, peritoneal macrophages co-stimulated with 1 microgram of lipopolysaccharide (LPS) and 10(-10) M MENK potentiated IL-1 activity, compared to LPS alone, but abrogated TNF activity induced by LPS. While MENK alone slightly decreased phagocytosis of sheep red blood cells (SRBC) by mouse peritoneal macrophages, cells simultaneously incubated with 1 microgram of LPS and 10(-10) M MENK had increased phagocytosis compared to LPS alone. Moreover, phagocytosis of SRBC by cells incubated overnight with the supernatant of the respective cell culture was significantly augmented. These results provide additional evidence for the immunoregulatory role of neuropeptides and suggest that the modulatory action of MENK could be mediated, at least in part, through the up-regulation of cytokines, most probably IL-1 and TNF.

Animals↗
PubMed1993

Met-enkephalin induced escape from dexamethasone immunosuppression.

The present study was undertaken to examine whether and what type of interaction occurs between a synthetic glucocorticoid, dexamethasone (DEX) and an opioid peptide, met-enkephalin (MENK) upon superoxide anion (O2-) release from human polymorphonuclear cells (PMN). MENK (10(-8) M) abolished suppressed O2- release from PMNs treated with 10(-7) M DEX. This was the case in unstimulated but not in PMNs stimulated with PMA. The effect of MENK was mediated through pertussis-toxin (PTX) sensitive G-protein and since it was abolished by H7 probably involves protein kinase C (PKC) as a second messenger system. Thus, MENK can abolish DEX induced suppression of O2- release from human PMNs possibly through the interaction of second messenger pathways.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

A characterization of the in vivo immunomodulation by Met-enkephalin in mice.

Single intraperitoneal injections of Met-enkephalin (MENK) into CBA mice decreased the phagocytic activity of peritoneal macrophages, Con-A-induced proliferation and NK-activity of spleen cells. Conversely, in mice which had been immunized with sheep erythrocytes, treatment with MENK was associated with enhancement of phagocytosis, and no effect on lymphoid proliferation and NK-cytotoxicity of spleen cells. MENK-induced inhibition of cellular functions in nonimmunized mice was associated with a decrease of plasma ACTH level, whereas MENK-induced stimulation of phagocytosis in immunized mice was paralleled with an elevation of ACTH, suggesting a role of corticoids in immunomodulation by MENK. MENK-induced modulation (suppression and stimulation) of phagocytosis, as well as inhibition of spleen cell proliferation, was not observable in adrenalectomized mice, although a reduced NK-cytotoxicity was still present.

Adrenal Glands↗
PubMed1993

The effect of Met-enkephalin on mice liver lysosomes.

The unsedimentable activities of acid phosphatase (AP) and beta-glucosidase (BG), from mice liver lysosomes significantly increased 6 h after a single i/p injection of Met-enkephalin (MENK). The activity of AP in the serum at the same time remained unchanged. Multiple injections of MENK (8 x 10 mg/kg) induced a significant decrease in AP activity in the serum and no change in the unsedimentable activities of AP or BG. MENK did not elicit any significant extracellular release of lactate dehydrogenase (LDH) either, indicating that, under the experimental conditions described, the cells remained intact. Other parameters, such as the activities of AP and BG in the liver and total sialic acid content in the serum and spleen remained unaltered. Moreover, MENK in concentrations of 10(-12) M, 10(-8) M, 10(-6) M or 10(-4) M did not change the activities of the lysosomal enzyme markers AP or BG in vitro. These data indicate far less pronounced transient effects of MENK on lysosomal membranes and enzymes compared to Leu-enkephalin which may be relevant for the use of MENK in combined chemo-immunotherapy.

Acid Phosphatase↗
PubMed1992

Interaction of Met-enkephalin and corticosteroids in immunomodulation.

The effect of Met-enkephalin (MENK) on several immune functions, corticosterone (CS) and adrenocorticotropin (ACTH) levels in the plasma was studied in adrenalectomized (ADX) and sham-adrenalectomized (SADX) mice. Multiple Met-enkephalin injections (10 mg/kg per day in two injections 12 h apart, for 4 days) increased the plaque-forming cell response to sheep erythrocytes in the spleen and enhanced the proliferation of spleen cells in vitro. These effects were comparable in sham-adrenalectomized and adrenalectomized mice. However, spleen cells of mice immunized with sheep red blood cells and injected with Met-enkephalin, showed suppressed blastogeneic transformation with Con A. The effect was equal in adrenalectomized and sham-adrenalectomized mice. In the absence of Con A in spleen cell cultures, MENK treatment of donor mice resulted in a significant mitogenic effect. NK activity of the spleen cells was suppressed in MENK-treated adrenalectomized mice. Injection of MENK decreased corticosterone levels and increased ACTH levels in the plasma of sham-adrenalectomized mice. In adrenalectomized mice plasma levels of ACTH were decreased by MENK. It seems that corticosteroid secretion, although changed by adrenalectomy and influenced by treatment with MENK, does not influence the modulatory effect of MENK on the PFC response and blastogeneic transformation of mouse spleen cells. However, NK activity of the spleen cells treated with MENK seems to the reflect joint action of MENK and corticosteroids.

Adrenalectomy↗
PubMed1992

Effect of enkephalins on bone marrow cells.

Mouse bone marrow cells were incubated with methionine- or leucine-enkephalin (10(-15)-10(-6) M) before seeding into soft agar cultures. In marrow samples harvested at different times, enkephalins decreased GM colony count on average by 30-40%. In individual experiments, however, the same concentration of enkephalins caused even stimulation, or at other times had effect. In view of the circadian periodicity of neuroendocrine functions and hematopoietic activity, the enkephalin effect on bone marrow cells was tested on marrow samples harvested at fixed time points (6 am, 6 pm), using enkephalin concentrations in the physiological range (10(-12)-10(-9) M). The seeding efficiency of the 6-pm cell population was on average 50% above that of the 6-am population. The 6-pm cell population was also more susceptible to the inhibitory effect of the enkephalins (35% inhibition) than the 6-am population (15% inhibition), and the variability in response was considerably reduced. With progenitor cell-enriched population, obtained by fluorescence-activated cell sorting (FACS) of 6-am bone marrow samples, in 3 out of 6 experiments Met- and Leu-enkephalin showed 30-35% inhibition of GM colony formation over a wide range of concentrations (10(-15)-10(-6)). In the other 3 experiments, suppression as well as stimulation or no alteration in colony count were observed. This variability probably reflected quality (purity) of the progenitor cell population, and may indicate that the enkephalins affected hematopoietic cells via a population of accessory cells.

Analysis of Variance↗
PubMed1992

Naloxone is an inappropriate antagonist of met-enkephalin-modulated superoxide anion release.

Met-enkephalin (MENK) increased superoxide anion release by human polymorphonuclear cells (PMNs) at a physiological (10(-10) M) concentration and decreased release at a relatively high (10(-8) M) concentration. Surprisingly, naloxone (NAL), used as a specific antagonist in these experiments, displayed immunomodulatory actions of its own, increasing superoxide anion release at 10(-10) and 10(-8) M concentrations. Although both were effective, the dose-response curves were different for NAL and MENK. NAL and MENK also had a combined influence on O2- release. The stimulative effect of 10(-10) M MENK could be abolished by 10(-8) M NAL in seven of eight cases. Unexpectedly, the stimulatory effect of 10(-8) and 10(-10) M NAL could be abrogated by MENK in five of eight cases as well. The fact that NAL and MENK mutually interfere with one another in their effect upon O2- release by human PMNs discredits NAL as an appropriate antagonist in this system.

Adult↗
PubMed1991

Affinity labeling of the membrane protein-binding component of human polymorphonuclear leukocyte receptors for leukotriene B4.

A radiolabeled N-(3-aminopropyl)-leukotriene B4 amide ([3H]LTB4-APA) analog of the potent leukocyte chemotactic factor leukotriene B4 (LTB4) binds to receptors for LTB4 in plasma membrane-enriched preparations from human blood polymorphonuclear leukocytes (PMNL) and intact PMNL with respective mean dissociation constants of 2.3 nM and 69 nM at 4 degrees C. The [3H]LTB4-APA bound to plasma membrane-enriched preparations from PMNL was covalently cross-linked to membrane proteins with disuccinimidyl suberate. Solubilization and resolution by SDS-PAGE of proteins from [3H]LTB4-APA-labeled PMNL membranes revealed predominant labeling of a 60-kDa protein. Labeling of the PMNL membrane protein was inhibited by LTB4 and its analogs at concentrations similar to those inhibiting the binding of [3H]LTB4 to its receptor, with an identical rank order of potency of LTB4 greater than 20-hydroxy-LTB4 greater than LTB4-APA = 5(S),12(R)-dihydroxy-eicosa-14-cis-6,8,10-trans-tetraenoic acid much greater than LTD4 = LTC4. GTP suppressed the labeling of the 60-kDa PMNL membrane protein to an extent consistent with the decrease in receptor affinity for LTB4 induced by GTP. The stereospecificity of the affinity cross-linking reaction and the regulation by GTP support the identification of an approximately 60-kDa protein as the binding component of the PMNL receptor for LTB4.

Affinity Labels↗
PubMed1991

Effect of pentoxifylline on superoxide anion production by human sperm.

The in-vitro effect of pentoxifylline, a methylxanthine derivative, on superoxide anion generation by sperm was studied in 27 men with superoxide anion production ranging from 0.57 to 13.8 nmoles 02-. per 10(6) sperm. Superoxide anion release stimulated by phorbol myristate acetate, a potent activator of oxygen radical generation, was reduced by 29-72% following the addition of 10 mM pentoxifylline. The inhibitory effect of this millimolar concentration of the drug did not depend on the initial superoxide production in the presence of phorbol myristate acetate. These results point to a potential use for pentoxifylline in the treatment of male infertility in men with an increased superoxide anion generation capacity.

Cell Membrane↗
PubMed1990

Leu-enkephalin induced alteration of enzymes and sialic acid levels in vivo.

The influence in mice of 10 mg/kg Leu-enkephalin (LENK) on the activity of hepatic enzymes in serum and liver and sialic acid concentration in serum and spleen is described. The activity of acid and alkaline phosphatase and lactate dehydrogenase in serum was significantly enhanced 6 h after a single (10 mg/kg) LENK injection. This effect was not dose-dependent. The increase of acid phosphatase in serum was accompanied by a simultaneous decrease in the liver. While the level of serum sialic acid remained unchanged, it decreased in the spleen 6 h after a single LENK injection. The effect of LENK in the spleen and liver was dose-dependent; ie, the higher the dose the greater the effect. Multiple injections of Leu-enkephalin (6 x 10 mg/kg) induced the same degree of increase but an earlier rise in serum alkaline, acid phosphatase and lactate dehydrogenase levels than with a single injection. This was not accompanied by a change of activity in liver and spleen. These data may be relevant for use of LENK in combined chemo-immunotherapy, since liver enzyme changes may alter drug metabolism, and since sialic acid plays a regulatory role in immune processes.

Acid Phosphatase↗
PubMed1990

Modulation of superoxide anion release from human polymorphonuclear cells by Met- and Leu-enkephalin.

The present work describes the ability of Met- and Leu-enkephalin to modulate the superoxide anion (O2-) release from unstimulated human polymorphonuclear cells (PMN) and from PMN stimulated with phorbol myristate acetate (PMA). The direction (stimulation or suppression) and the magnitude of change were dependent upon the baseline reactivity of the donor's PMN. Both opioid peptides stimulated O2- release by PMN from donors with low baseline reactivity in a concentration-dependent manner. PMNs collected from donors with medium baseline reactivity incubated with Leu-enkephalin regardless of concentration released less O2- than control, nontreated PMNs. Met-enkephalin stimulated O2- release but only at 2 X 10(-15) M concentration. Superoxide anion release from PMNs of individuals with high baseline reactivity was concentration dependent and suppressed by Met- and Leu-enkephalin. Leu-enkephalin induced baseline reactivity was dependent upon progressive increase in the magnitude of change on O2- release (i.e., the higher the baseline the higher the magnitude of change in O2- generation). Met-enkephalin data show this also, but to a lesser extent. In cells stimulated with PMA, Met-enkephalin caused additional O2- release, while Leu-enkephalin was ineffective in triggering already stimulated cells. The modulating effect of both opioid peptides on superoxide anion release by human PMN is a short phenomenon that lasts up to 10 min after the addition of the peptide.

Anions↗
PubMed1987

Suppression of immune response in rats by stress and drugs interfering with metabolism of serotonin.

Rats immunized with sheep erythrocytes were stressed by repeated restraint and/or treated with a precursor of serotonin (5-hydroxytryptophan, 5-HTP) or with an inhibitor of serotonin synthesis (parachlorophenylalanine, PCPA). As expected, repeated stress reduced the plaque-forming cell (PFC) response. Treatment with 5-HTP also reduced the PFC response, and potentiated the immunosuppressive effect of stress. This was accompanied by increased metabolism of serotonin in the brain, as indicated by increased concentration of its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in cerebral tissue. Treatment with PCPA also suppressed the PFC response, but this suppression was accompanied by decreased levels of brain serotonin and of 5-HIAA. Plasma corticosterone levels were elevated, reaching statistical significance, in rats treated with PCPA. Both drugs suppressed the in vitro PFC response of peripheral blood lymphocytes. Thus, although 5-HTP and PCPA altered serotonin metabolism in the brain in a diametrically opposite manner, their effects on the immune response were the same. Putative central effects of the drugs on serotoninergic regulation of the immune response were apparently obscured by their effects on corticosterone secretion as well as by their direct effects on immunocompetent cells.

Animals↗
PubMed1987

Molecular and cellular properties of human polymorphonuclear leukocyte receptors for leukotriene B4.

The distinctive characteristics of human polymorphonuclear (PMN) leukocyte receptors for leukotriene B4 (LTB4) have been elucidated by studies of binding of [3H]LTB4, the structure of protein constituents of the receptors isolated from plasma membranes, and the effects of antireceptor antibodies. A high-affinity class of 4400 receptors with a KD of 0.4 nM mediates chemotaxis and increased adherence of PMN leukocytes, whereas a low-affinity class of 270,000 receptors with a KD of 61 nM mediates the release of lysosomal enzymes and increases in oxidative metabolism. The low-affinity receptors are composed of a 60,000-dalton protein-binding unit. The high-affinity receptors are composed of the same binding unit in association with a 40,000-dalton guanine nucleotide-binding protein. That antireceptor antibodies as well as LTB4 distinguish the two classes of receptors with different functional consequences suggests the possibility of unique approaches to the regulation of leukocyte function at the receptor level.

Antibodies, Monoclonal↗
PubMed1984

Recovery of the immune system in diabetic mice after transplantation of isolated islets of Langerhans.

Adult CBA/HZgb mice islets harvested by collagenase digestion were injected intraperitoneally in 52 singeneic diabetic recipients (CBA/Hgb leads to CBA/HZgb, 450-600 islets per mouse). Normal serum glucose levels, 24-h urine volume, insulin levels and body weight were completely restored to normal in all recipients during the next 2-5 months. Immunological function was assessed in control, diabetic and diabetic-transplanted mice by following their responses to sheep erythrocytes (expressed as the number plaque-forming cells in the spleen). In transplanted mice, the plaque-forming cell responses were as follows: 1 month after transplantation--43% of the plaque-forming cell counts in control (normal, non-diabetic) mice; 2 months after transplantation--56% of the control value; and 94% of the control value after 5 months. Ten months after the transplantation, the plaque-forming cell counts were slightly above the control value (148%). It appears, therefore that transplantated islet tissue positively affects the immunological as well as the diabetic state of the recipients.

Animals↗