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M De La Fuente

Publications and source records attributed to M De La Fuente.

11 recordsLinked to original sources
PubMed2003

Changes in the superoxide production and other macrophage functions could be related to the mortality of mice with endotoxin-induced oxidative stress.

Free radicals and proinflammatory cytokines from phagocytes have been implicated in the pathogenesis of endotoxic shock, a disease with high mortality caused by Gram-negative bacterial endotoxin. In the present study, male BALB/c and Swiss mice received intraperitoneally lipopolysaccharide (LPS) at 100 mg/kg and 150 mg/kg, respectively, that led to a lethal endotoxic shock (100 % of mortality before 30 h). Swiss mice injected with 100 mg/kg, that did not show lethal endotoxic shock, were also studied. Peritoneal macrophages were obtained from animals at 2, 4, 12 or 24 h after injection of LPS or saline (control) solutions. Superoxide anion and tumor necrosis factor (TNFalpha) production were determined in these cells as well as other functions such as adherence capacity, chemotaxis and phagocytosis. The increase in superoxide anion production after endotoxin injection was higher in cells from mice with lethal shock than in those with non-lethal shock. However, the enhancement of TNFalpha production was similar in all cases, although in Swiss mice the highest levels of TNFalpha were observed at 1.5 h after endotoxin injection, while in BALB/c mice they occurred at 2 h after LPS injection. This oxidative stress was also revealed by the other functions analyzed, since adherence to substrate and phagocytosis were stimulated and chemotaxis was decreased after endotoxin injection as compared to controls, the differences being even more significant in animals with lethal shock. These data suggest that these changes, mainly the increased production of free radicals even more than the TNFalpha release, could be involved in mouse mortality caused by LPS.

Animals↗
PubMed2002

A diet supplemented with thiolic anti-oxidants improves leucocyte function in two strains of prematurely ageing mice.

1. According to previous studies, Swiss mice of the same age showed striking interindividual differences in behaviour when exposed to a T-maze test, with a slow performance being linked to an impaired immune function, hyperemotional response to stress and a shorter life span compared with mice that quickly explore the maze. These facts led us to propose the slow mice as a model of prematurely ageing mice (PAM). 2. In the present study, we investigated whether this prematurely ageing model could be found in other strains of mice, such as BALB/c mice, by analysing several lymphocytes functions, such as adherence, chemotaxis, proliferative response to the mitogen concanavalin A (Con A), interleukin (IL)-2 release and natural killer (NK) activity. In addition, we tested the probable beneficial effects on these functions of dietary supplementation with thioproline (TP) plus N-acetylcysteine (NAC; 0.1% w/w of each anti-oxidant) in female Swiss and BALB/c mice. 3. Our model of premature ageing, previously reported in Swiss mice, has also been reproduced in the inbred BALB/c mouse strain, in which PAM showing an immunosenescence in several lymphocyte functions, such as lower chemotaxis, proliferative response to Con A, IL-2 release and NK activity, as well as higher adherence, were observed. A short-term (5 week) ingestion of TP + NAC by female Swiss and BALB/c mice improved leucocyte function, increasing chemotaxis, the proliferative response to Con A, IL-2 release and NK activity and decreasing the adherence of lymphocytes. These effects are greatest in cells from PAM of both strains. 4. In conclusion, our model of premature ageing has been reproduced in an inbred strain. In addition, the ingestion of a diet supplemented with two thiolic anti-oxidants, such as NAC and TP, has been shown to be beneficial to the immune response in PAM.

Acetylcysteine↗
PubMed2002

The amount of thiolic antioxidant ingestion needed to improve several immune functions is higher in aged than in adult mice.

With aging there is an increase of oxidative stress due to an imbalance between the oxidant production and the antioxidant levels in favor of the former. Since immune cell functions are specially linked to reactive oxygen species (ROS) generation, the oxidant/antioxidant balance is essential for these cells. Although low levels of antioxidants cause a decrease in immune function, very high levels of antioxidant compounds could show prooxidant effects. In the present work, we have studied the effect of diet supplementation, for 4 weeks, with two different doses of two thiolic antioxidants, namely thioproline (TP) and N-acetylcysteine (NAC), at 0.1% (w/w) and 0.3% (w/w, of each antioxidant) on the main immune system cells, i.e.: macrophages, lymphocytes and natural killer (NK) cells of adult (33+/-1 week old) and aged (75+/-1 week old) female Swiss mice. Two groups of animals, adult and aged mice, fed standard diet were used as controls. The results show that the ingestion of 0.1% doses of thiols improves, in the adult mice, several immune functions such as the chemotaxis capacity of both macrophages and lymphocytes, the phagocytosis of macrophages, the lymphoproliferative response to the mitogen Con A and the NK activity. Moreover, no change was observed in adherence capacity of immune cells, and superoxide production was decreased. By contrast, in aged mice the ingestion of these amounts of antioxidants did not change the immune functions studied with the exception of NK activity, which was stimulated. The ingestion of 0.3% of antioxidants by adult mice only increased some immune functions such as adherence and superoxide production, which are markers of oxidative stress. Other functions such as chemotaxis or lymphoproliferative response decreased. However, the ingestion of these very high amounts of thiols by aged animals increased the phagocytosis, the NK activity and specially the lymphoproliferative response to the mitogen, a function that is very depressed with aging.

Acetylcysteine↗
PubMed2000

Ageing modulates some aspects of the non-specific immune response of murine macrophages and lymphocytes.

The deterioration of the immune system with ageing, which leads to an increased morbidity and mortality from infections, appears to be related to decreases in specific lymphocyte functions. However, the alteration of non-specific immunity is a more controversial subject. Our purpose was to investigate the age-related changes of different functions of the non-specific immune response in peritoneal macrophages (adherence to tissues, mobility directed to a chemical gradient from an infectious focus or chemotaxis, phagocytosis of foreign agents and destruction of these agents by superoxide anion production) and in lymphocytes (adherence and chemotaxis) from peritoneum, axillary lymph nodes, spleen and thymus. We used young (12 weeks), adult (22 weeks), mature (48 weeks) and old (72 weeks) female BALB/c mice. The adherence capacity of macrophages and lymphocytes was greater in adult and old mice than in young animals. The chemotaxis of macrophages showed higher values in cells from young mice than in those from adult mice, increasing again in macrophages from mature and old animals. A similar behaviour was shown by phagocytosis, which reached its highest values in old animals. Anion superoxide production increased with age and again the highest values were obtained in the oldest mice. Conversely, chemotaxis of lymphocytes was higher in the adult and mature animals than in the young and old animals. We conclude that, although there is a decrease in lymphocyte chemotaxis in old animals, the non-specific immune response of macrophages instead of decreasing, may increase in aged mice with respect to the values seen in adult mice.

Aging↗
PubMed1999

Improvement of murine immune functions in vitro by thioproline.

Previous studies have shown that several immune functions were improved in mice after the ingestion of a thioproline (thiazolidine-4-carboxylic acid) enriched diet. In the present work, we have studied the in vitro effects of several concentrations of this thiol compound (0.1, 0.5, 1, 2.5 and 5 mM) on the most relevant functions of three pivotal immune cells, namely, macrophages, lymphocytes, and natural killer (NK) cells from BALB/c mice. The results show that thioproline stimulates the phagocytic process of macrophages, increasing the mobility directed to the inflammatory focus (chemotaxis) and the phagocytosis of inert particles. It increases the adherence and the chemotaxis capacities of lymphocytes, their proliferative activity and favours the natural cytotoxic activity that could improve the capacity to destroy malignant cells. Thioproline concentrations of 0.5 and 1 mM were the most effective regarding the different functions analysed. These results suggest that the improvement of immune functions, observed in previous work, after thioproline-enriched diet ingestion is due to a direct action of this thiol compound on immune cells.

Animals↗
PubMed1997

Effect of cholecystokinin and gastrin on human peripheral blood lymphocyte functions, implication of cyclic AMP and interleukin 2.

The effects in vitro of sulphated and desulphated cholecystokinin (CCK)-8, and of gastrin-17 and gastrin-34 were studied at concentrations from 10(-14) M to 10(-6) M on several functions of human peripheral blood lymphocytes, i.e.: adherence to substrate, mobility (spontaneous and directed by a chemical gradient or chemotaxis), and spontaneous and phytohaemagglutinin (PHA)-mediated proliferation. All peptides, at concentrations from 10(-10) M to 10(-8) M, inhibited significantly the mobility capacity and PHA-induced proliferation, and increased the adherence and spontaneous proliferation. A dose-response relationship was observed, with a maximum response of lymphocyte functions at 10(-10) M. These peptides induced a significant increase of intracellular cAMP levels at 30 and 60 sec. Because lymphoproliferation requires production of interleukin 2 (IL-2) by lymphocytes, we also measured the IL-2 production in the presence of the CCK and gastrin peptides, finding that this production was higher than in the respective controls. When peptides were added to samples containing PHA, the IL-2 production was significantly decreased with respect to samples incubated with PHA alone. These results suggest that the CCK and gastrin peptides are negative modulators of lymphocyte mobility (spontaneous mobility and chemotaxis), causing an inhibition of these activities through an increase of intracellular cAMP levels, and of PHA-induced lymphoproliferation, which is mediated by a diminution of the IL-2 production by lymphocytes.

Adult↗
PubMed1985

Changes in the macrophage function with aging.

Changes in the adherence, opsonization, phagocytosis, nitroblue tetrazolium reduction and antibody-dependent cell cytotoxicity of peritoneal macrophages were observed with aging in BALB/C mice. A decrease in all the parameters studied, except for the reduction capacity of nitroblue tetrazolium, which increased with aging, was found in the long-lived mice. The role of the macrophage in immune hyporesponsiveness with aging is discussed.

Aging↗
PubMedDate not supplied

Influence of physical activity stress and age on the ADCC of lymphocytes from mice.

The influence of physical activity stress (swimming until exhaustion) and age on the antibody-dependent cellular cytotoxicity (ADCC) of lymphocytes from spleen, thymus and axillary lymph nodes in BALB/c mice was studied. The results indicate that the ADCC activity decreases after the acute stress both in young and in old mice. However, when swimming until exhaustion is performed after 1 month training, the ADCC activity increases except in the case of spleen lymphocytes from old mice. The basal ADCC capacity of spleen lymphocytes from old controls is higher (P<0.05) than from young controls, but there are no statistically significant differences in this respect between young and old animals in lymphocytes from thymus and axillary lymph nodes. No correlations between the increase in serum corticosterone levels and ADCC response are found.

Journal Article↗