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Biomedical subjects

L F Costa Rosa

Publications and source records attributed to L F Costa Rosa.

18 recordsLinked to original sources
PubMed2001

Melatonin modulates allergic lung inflammation.

Asthma is an inflammatory lung disease characterized by cell migration, bronchoconstriction and hyperresponsiveness, and can be induced, as an experimental model, by ovalbumin sensitization followed by a challenge. In addition to the well-known immunostimulatory effects of melatonin, research has identified some of its anti-inflammatory properties. In this study, we evaluated the influence of pinealectomy and melatonin administration on cell migration in an experimental model of allergic airway inflammation. We evaluated, in pinealectomized rats treated or not with melatonin, cell migration into the bronchoalveolar fluid, the number of cells and their proliferative activity in the bone marrow, and plasma corticosterone levels. Pinealectomy reduces, 24 hr after the challenge, the total cell number count in the lung and bone marrow cell proliferation, without changing the number of cells in the bone marrow or in the peripheral blood. This fact suggests that melatonin is important in the control of cell recruitment from the bone marrow and the migration of those cells to the lung. Melatonin administration to pinealectomized rats seems to restore the ability of cells to migrate from the bone marrow to the bronchoalveolar fluid. So, the development of specific inhibitors of melatonin would benefit patients with asthma.

Animals↗
PubMed2000

Effect of a moderate intensity exercise training protocol on the metabolism of macrophages and lymphocytes of tumour-bearing rats.

It is commonly accepted that moderate intensity exercise is beneficial to the immune system. We tested the influence of a moderate intensity training protocol (8 weeks) upon immune system function in Wistar tumour-bearing (TB) rats. The metabolism of glucose and glutamine in lymphocytes and macrophages was assessed, together with some functional parameters (hydrogen peroxide production and lymphocyte proliferative response). These substrates were chosen since they represent the most important energetic and synthetic metabolites for these cellular types. The training protocol caused a decrease of 17.4 per cent in the production of H(2)O(2) by macrophages, as well as a decrease in glucose consumption (25 per cent) and lactate production (47.1 per cent), and an increase in the production of labelled CO(2) from the oxidation of [U-(14)C]-glucose, in TB rats. The training protocol was also able to induce changes in the maximal activity of some key enzymes in the metabolism of glucose and glutamine, a reduction of hexokinase (68.8 per cent) activity and an increase in the activity of citrate synthase (10.1 per cent) in TB rats. The training protocol increased the proliferative response of lymphocytes cultivated in the absence of mitogens (75 per cent), of those cultivated in the presence of ConA (38.2 per cent) and in the presence of LPS (45.0 per cent). These cells also showed an increase in the maximal activity of some key enzymes of the glycolytic and glutaminolytic pathways. Our data demonstrated that the training protocol was able to induce an increase in aerobic utilisation of both substrates in lymphocytes and macrophages. The training protocol was also able to prevent several changes in glucose and glutamine metabolism that are normally present in sedentary TB rats. These changes in immune cell metabolism induced by the training protocol were able to increase TB rat survival.

Animals↗
PubMed2000

The effect of BCAA supplementation upon the immune response of triathletes.

INTRODUCTION: Intense long-duration exercise could lead to immune suppression through a decrease in the circulating level of plasma glutamine. The decrease in plasma glutamine concentration as a consequence of intense long-duration exercise was reversed, in some cases, by supplementing the diet of the athletes with branched-chain amino acids (BCAA). To better address this question, we have evaluated some blood parameters (lymphocyte proliferation, the level of plasma cytokines, plasma glutamine concentration, and in vitro production of cytokines by peripheral blood lymphocytes) before and after the São Paulo International Triathlon, as well as the incidence of symptoms of infections between the groups. METHODS: Twelve elite male triathletes of mean age 25.5 +/- 3.2 yr (ranging from 21.4 to 30.1 yr), weighing 74.16 +/- 3.9 kg, swam 1.5 km, cycled 40 km, and ran 10 km (Olympic triathlon) in the São Paulo International Triathlon held in April 1997 and April 1998. In both events, six athletes received BCAA and the others, placebo. RESULTS: Athletes from the BCAA group (BG) presented the same levels of plasma glutamine, before and after the trial, whereas those from the placebo group showed a reduction of 22.8% in plasma glutamine concentration after the competition. Changes in the proliferative response of peripheral blood lymphocytes were accompanied by a reduction in IL-1 production after exercise (22.2%), which was reversed by BCAA supplementation (20.3%), without changes in IL-2 production. DISCUSSION: The data obtained show that BCAA supplementation can reverse the reduction in serum glutamine concentration observed after prolonged intense exercise such as an Olympic triathlon. The decrease in plasma glutamine concentration is paralleled by an increased incidence of symptoms of infections that results in augmented proliferative response of lymphocytes cultivated in the absence of mitogens. The prevention of the lowering of plasma glutamine concentration allows an increased response of lymphocytes to ConA and LPS, as well as an increased production of IL-1 and 2, TNF-alpha, and IFN-gamma, possibly linked to the lower incidence of symptoms of infection (33.84%) reported by the supplemented athletes.

Adult↗
PubMed1999

The effect of adrenaline and Walker-256 tumour-induced cachexia upon Kupffer cell metabolism.

Kupffer cells (KC), the liver macrophages, are able to produce PGE(2), which is involved in immune suppression and in the aggravation of cancer cachexia due to interference with lipid metabolism in the liver. Since tumour-bearing (TB) rats present high plasma epinephrine levels, and this hormone is able to affect macrophage metabolism and function, we have assessed the effect of epinephrine (5 nM) upon Kupffer cell PGE(2) production. Epinephrine induced increased production of PGE(2) both by control (3.5-fold) and TB rats (27 per cent) KC, an effect blocked by propranolol. Enhancement of cAMP content in the cells by addition of isoproterenol (0.1 microM) to the incubations, however, failed to induce the same response in the cells. Nevertheless, when phenylephrine (1 microM) was added to the incubation, a similar pattern of PGE(2) production to that observed for epinephrine was found for control and TB rat KC. We propose that the effect of epinephrine upon KC PGE(2) production is mediated by alpha-adrenergic receptors and that Ca(2+) is involved in the response, since increasing concentrations of the ion added to the incubation medium (0.25, 0.5 and 1.0 mM) enhanced the eicosanoid production, while EDTA abolished the response.

Adrenergic alpha-Agonists↗
PubMed1999

Metabolic response of macrophages to injury promoted by the activated complement system.

In nucleated cells, the swelling promoted by a complement system (CS) attack is not enough to promote cell death, because unlike erythrocytes these cells are able to eliminate cytolytic complement channels from the plasma membrane, by processes that include endocytosis. Several studies have demonstrated that the resistance of nucleated cells to the injury promoted by the CS is related to the cellular metabolism. Despite this, to the present day, no study has clearly related cell survival capacity to injury by the CS to its energetic metabolic status. In macrophages, the challenge imposed by the CS provoked an increase in the total amount of glucose incorporated into fatty acids, including phospholipids and cholesterol; substrates for membrane synthesis. The inhibition of cholesterol synthesis promoted an increase of the cell death rate. These data support the importance of cholesterol metabolism for macrophage resistance to necrosis induced by the activated complement system.

Acetates↗
PubMed1998

The effect of melatonin chronic treatment upon macrophage and lymphocyte metabolism and function in Walker-256 tumour-bearing rats.

Melatonin is the main hormone involved in the neuroendocrine-immune axis. It also presents antitumour activity. To evaluate the role of melatonin on the progression of Walker-256 tumour in rats we determined the effect of the hormone on some biochemical and functional aspects of macrophage and lymphocytes from cachectic rats. An important finding observed in immune cells from tumour-bearing (TB) rats is the impairment on glutamine and glucose metabolism in such cells. These changes are very similar to those observed in pinealectomized rats (PNX). The increased production of lactate and the flux of glucose through the Krebs cycle and the reduction in glutamine consumption seems to be involved in the immunosuppression presented in the TB and PNX animals. Melatonin treatment restored the changes observed in the metabolism of glucose and glutamine and stimulated the proliferation of lymphocytes from tumour-bearing rats. The results indicate that the effect of melatonin upon tumour growth involves the stimulation of the immune system by the hormone.

Animals↗
PubMed1996

The effect of insulin on macrophage metabolism and function.

This study examined the effect of insulin on rat macrophage metabolism and function. The following parameters were studied: cell migration in response to thioglycollate and BCG stimuli, macrophage phagocytic capacity, H2O2 production, glucose and glutamine metabolism as indicated by the measurement of enzyme activities, the utilization of metabolites and production and oxidation of substrates. The results indicate that insulin: (1) did not affect cell migration in response to thioglycollate and BCG; (2) enhanced the phagocytic capacity of macrophages and the production of H2O2 by macrophages; (3) increased the metabolism of glucose and reduced that of glutaminase.

Alloxan↗
PubMed1996

Metabolism of glucose and glutamine in lymphocytes from Graves' hyperthyroid patients: influence of methimazole treatment.

Several studies have shown that thyroid hormones are able to influence selected immune responses such as cell mediated immunity, differentiation of B lymphocytes and the activity of NK cells. These hormones can also regulate the metabolism of glucose and glutamine in rat macrophages and their effects seem to occur mainly through the Krebs cycle. Alterations in the hexokinase, citrate synthase, glucose-6-phosphate dehydrogenase and glutaminase activities in lymphocytes from patients with Graves' disease, either untreated or on methimazole (MMI) therapy were investigated. Experiments were also done in vitro to determine the activities of these enzymes in normal lymphocytes cultured for 24 h in the presence of MMI T3 and T4 using concentrations close to the physiological. Changes in the conversion of [U-14C]-glucose and [U-14C]-glutamine to 14CO2 as caused by the addition of MMI, T3 or T4 to the culture medium were also evaluated. The results indicate that high levels of thyroid hormones might stimulate the metabolism of glucose and glutamine for a short period of time but, if the stimulus is maintained, the utilization of glutamine by lymphocytes is then suppressed. Moreover, MMI does affect lymphocyte metabolism but the significance of this finding for its immunosuppressive effect remains to be examined.

Adult↗
PubMed1996

Glutamine metabolism is changed in lymphocytes from aged rats.

Changes in the protein content, maximal activity, and Km of phosphate-dependent glutaminase were measured in the lymphoid organs (thymus, spleen, and mesenteric lymph nodes) from just-weaned, mature (3 months), and aged rats (15 months). Also, [U-14C] glutamine transport and decarboxylation and the production of glutamate and aspartate from 2 and 20 mM glutamine were measured in incubated mesenteric lymph node lymphocytes. The ageing process induced a reduction in the protein content of the thymus and spleen, as well as the phosphate-dependent glutaminase activity in the thymus and isolated lymphocytes. The Km of phosphate-dependent glutaminase, however, was not affected by the process. Ageing reduced [U-14C] glutamine decarboxylation and increased glutamate and aspartate production in incubated lymphocytes. The results indicate that the ageing process does modify several aspects of glutamine metabolism in lymphocytes: reduces maximal glutaminase activity and [U-14C] glutamine decarboxylation and increases the Km for [U-14C] glutamine uptake and the production of glutamate and aspartate.

Aging↗
PubMed1996

The effect of N-3 PUFA rich diet upon macrophage and lymphocyte metabolism and function.

A large body of evidence from experimental studies has documented that n-3 fatty acids can modify a variety of cell functions and disease states. As lymphocytes and macrophages are important cells for the development of the inflammatory and non-inflammatory immune response and are known to utilize high rates of glucose and glutamine, we have evaluated the effect of n-3 PUFA rich diet on the metabolisation of glucose and glutamine these cells, as well as the effect of one such diet upon the proliferative response of lymphocytes and the phagocytic capacity and hydrogen peroxide production by macrophages. The diet provoked an increase in the flux of glucose through the Krebs cycle in macrophages as well as a reduction in G6PDh and glutaminase activity in these cells. Lymphocytes from n-3 PUFA rich diet-fed rats showed a reduction in glucose and glutamine decarboxylation. Taken together the data show that, at least in part, the functional changes observed in macrophages and lymphocytes from n-3 PUFA-rich diet fed rats are related to the effect of this diet upon glucose and glutamine metabolism, leading to immunosuppression.

Animals↗
PubMed1995

Effect of adrenaline and phorbol myristate acetate or bacterial lipopolysaccharide on stimulation of pathways of macrophage glucose, glutamine and O2 metabolism. Evidence for cyclic AMP-dependent protein kinase mediated inhibition of glucose-6-phosphate dehydrogenase and activation of NADP+-dependent 'malic' enzyme.

Adrenaline has recently been shown to stimulate both glucose metabolism and H2O2 release by macrophages but the activity of the key pentose phosphate pathway enzyme, glucose-6-phosphate dehydrogenase (which generates the NADPH crucial for the reduction of molecular oxygen), was reduced under these conditions [Costa Rosa, Safi, Cury and Curi (1992) Biochem. Pharmacol. 44, 2235-2241]. We report here that adrenaline activates another NADPH-producing enzyme, NADP(+)-dependent 'malic' enzyme, while also inhibiting glucose-6-phosphate dehydrogenase, via cyclic AMP-dependent protein kinase (PKA) activation. Regulation of glucose-6-phosphate dehydrogenase activity by PKA has not been reported elsewhere. The sparing of some glucose from pentose phosphate pathway consumption may be important in the provision of glycerol 3-phosphate which in the macrophage may be required for new phospholipid synthesis. Glutamine oxidation was also stimulated by adrenaline thus providing increased substrate (malate) for NADP(+)-dependent 'malic' enzyme and therefore shifting some of the burden of NADPH production from glucose to glutamine metabolism. We also report a novel synergistic effect of adrenaline and some bacterial products and/or gamma-interferon in stimulating secretory and metabolic pathways in macrophages which may be a part of a larger network of signals that lead to enhanced macrophage activity.

Animals↗
PubMed1994

Effect of thioglycollate and BCG stimuli on glucose and glutamine metabolism in rat macrophages.

The macrophage is a differentiated cell that takes part in a wide range of physiological and pathological processes, such as inflammatory and immunological responses. The stimulation of macrophages involves the acquisition of some functional characteristics such as phagocytosis, ability to kill tumor cells, and processing and presentation of antigens. In this study we have investigated the changes in macrophage glucose and glutamine metabolism as induced by stimulation by thioglycollate (inflammatory) and bacille Calmette-Guérin (BCG) (activated). The results showed an increase in hexokinase and citrate synthase activities, due to both stimulatory processes. One difference between inflammatory and activated cells is the higher rate of glucose oxidation in the latter. The activation with BCG, however, also led to an enhancement in glutamine metabolism that is not observed in the inflammatory cell. These results suggest that glutamine metabolism might be important for macrophage function during immunological response.

Animals↗
PubMed1994

Superoxide dismutase, catalase, and glutathione peroxidase activities in muscle and lymphoid organs of sedentary and exercise-trained rats.

The effect of swimming-training upon the activities of the enzymes involved in the generation of reducing-equivalents (citrate synthase-mitochondria and glucose-6-phosphate dehydrogenase-cytosol) and of antioxidant enzymes (CuZn- and Mn-SOD, catalase and glutathione peroxidase) in the lymphoid organs (thymus, mesenteric lymph nodes and spleen) was examined. The skeletal muscles (soleus-red and gastrocnemius-white) were also studied. Although our data suggest an apparently random, organ-specific change in enzymatic activity, some interesting trends can be observed. Firstly, the increased citrate synthase and Mn-SOD activities observed in red, but not in white muscle, corroborate the well-known effect of endurance exercise-training on mitochondrial oxidative metabolism. Secondly, there was an inverse relationship between TBARs-monitored lipoperoxidation and glutathione peroxidase activity in all tissues studied, what is in accordance with the previous findings showing that such enzyme exerts the fine control of intracellular lipoperoxide concentration. Except in the case of the spleen, there was a trend for elevated glucose-6-phosphate dehydrogenase activity, coadjuvant of glutathione peroxidase in the antioxidant response to physical exercise in all tissues. Thirdly, Mn-SOD and catalase were conspicuously associated to oxidative stress in the thymus, while glutathione and catalase could be linked to this parameter in the spleen. Fourthly, the lymph nodes seem to be more dependent on the glucose-6-phosphate dehydrogenase/glutathione peroxidase pair for protection against damage promoted by physical exercise. Mn-SOD and catalase activities were lower in the lymph nodes after swimming training.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effect of epinephrine on glucose metabolism and hydrogen peroxide content in incubated rat macrophages.

The effects of epinephrine on glucose metabolism and hydrogen peroxide content were examined in incubated rat macrophages. An increase in the activities of hexokinase and citrate synthase and a reduction in that of glucose-6-phosphate dehydrogenase was found in resident, inflammatory and activated macrophages incubated for 1 hr in the presence of epinephrine. Glucose utilization by incubated resident, inflammatory and activated macrophages was augmented markedly by the addition of epinephrine, whereas lactate formation was depressed. Under the same conditions, there was a 2.6-fold increment of hydrogen peroxide content and of [U-14C]glucose decarboxylation in activated macrophages incubated for 40 min. Similar results were obtained when pyruvate and oxoglutarate was substituted for glucose. These findings suggest that epinephrine may increase hydrogen peroxide production in activated macrophages possibly through a mitochondrial mechanism other than the pentose-phosphate pathway. Between 40 and 90 min of incubation, the content of hydrogen peroxide decreased markedly, and there was no detectable glucose utilization in the presence of epinephrine. These observations are consistent with the idea that this catecholamine stimulates both hydrogen peroxide production and metabolism, the first process being dependent on mitochondrial fuels.

Animals↗
PubMed1992

Metabolic and functional changes in macrophages of rats fed polyunsaturated or saturated fatty acid rich-diets during ageing.

Previous reports from our laboratory showed that rats fed a polyunsaturated fatty acid-rich diet (UC), during an acute intervals, present important changes in macrophage metabolism and function, while a saturated fatty acid diet (SC) did not induce significant changes (10). In this study, two important questions were addressed: 1. the persistence of the changes induced by the UC and 2. the effect of a SC offered during ageing. The maximal activities of hexokinase, glucose-6-phosphate dehydrogenase, glutaminase, citrate synthase and glutathione peroxidase and the total content of lipid peroxides were measured in resident and inflammatory macrophages of rats fed control chow (CC), UC or SC during 14 months. Intraperitoneal cell migration by thioglycollate injection and the phagocytosis capacity were also evaluated. The results indicate that: 1) the changes caused by UC are exacerbated during ageing, and 2) the SC, given during a prolonged period of time, also caused important alterations of macrophage metabolism and function.

Administration, Oral↗
PubMed1991

Hormonal control of macrophage function and glutamine metabolism.

Murine macrophages have been reported to utilize glutamine at high rates. However, the role of glutamine in macrophage function is still unknown. In the present study, the maximum glutaminase activity of macrophages was investigated under several endocrine dysfunctions that are known to cause alterations in macrophage function. The results obtained suggest that glutamine might play an important role in the onset of phagocytosis in inflammatory macrophages. Moreover, the studies show that insulin, glucocorticoids, and thyroid hormones may be responsible for the regulation of glutamine metabolism and, consequently, of macrophage function.

Adrenalectomy↗
PubMed1991

Effect of polyunsaturated (PUFA n-6) and saturated fatty acids-rich diets on macrophage metabolism and function.

Previous reports of our laboratory have shown that PUFA (n-6)-rich diets cause important changes of the metabolism of the immune tissues. In this study, alterations of macrophage metabolism and function were examined in rats fed polyunsaturated (UC) or saturated (SC) fatty acids-rich diets during 6 weeks. The UC group decreased intraperitoneal cell migration and macrophage phagocytosis. These changes were related to modifications of macrophage metabolism. The UC group showed also increased G-6-PDh in inflammatory macrophages. These findings suggest that pentose-phosphate pathway is not the unique metabolic factor to control phagocytosis. PUFA-rich diet reduced glutaminase activity. Therefore, this amino acid might be one of the possible metabolic reasons for the impaired macrophage function observed.

Animals↗