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P C Calder

Publications and source records attributed to P C Calder.

At least 127 records · Page 7Linked to original sources
PubMed1993

Inhibition of lymphocyte protein kinase C by unsaturated fatty acids.

Oleic, arachidonic, eicosapentaenoic and docosahexaenoic acids inhibited lymphocyte protein kinase C activity in the presence of Ca2+, phospholipid and a phorbol ester. Linoleic and alpha-linolenic acids did not affect protein kinase C activity in this way and none of the fatty acids affected protein kinase A activity. These findings indicate direct inhibitory effects of some unsaturated fatty acids upon protein kinase C. Culture of lymphocytes in the presence of oleic, arachidonic, eicosapentaenoic or docosahexaenoic acids resulted in a reduction in protein kinase C activity (by up to 45%). Culture with linoleic or alpha-linolenic acids did not affect protein kinase C activity and none of the fatty acids affected total protein kinase A activity or the percentage in the active form. These results show for the first time that fatty acids have long term effects upon protein kinase C activity, perhaps as a result of altering the rate of turnover of the enzyme. It is suggested that the inhibition of lymphocyte functions caused by unsaturated fatty acids may in part be due to their effect on protein kinase C.

Animals↗
PubMed1993

Site-specific properties of human adipose depots homologous to those of other mammals.

1. Mean adipocyte volume, collagen content and the maximum activities of hexokinase and phosphofructokinase were measure in 15 depots of 8 men who were in good health until their sudden death. The data were used to establish homologies between depots in humans and other mammals. 2. The basic organization of adipose tissue in humans is similar to that of other mammals, although additional depots that are minimal or absent in rodents may be massive in humans. 3. Known site-specific properties relevant to manipulation of adipose tissue are reviewed.

Abdominal Muscles↗
PubMed1993

Propionate regulates lymphocyte proliferation and metabolism.

1. The effect of propionate on lymphocyte proliferation and metabolism was investigated. Lymphocytes obtained from human blood and rat mesenteric lymph nodes were utilized. 2. Propionate at concentrations of 0.04 and 1.0 mmol/l stimulated the amount of [3H]thymidine incorporated either in cultured human T lymphocytes or rat T and B lymphocytes. 3. Concentrations of propionate between 2 and 5 mmol/l caused a marked inhibition of lymphocyte proliferation. 4. This short-chain fatty acid was metabolized by these cells and produced succinate in significant amounts; however, its oxidation was low. 5. Propionate did not alter glucose, glutamine and pyruvate utilization and oxidation in incubated rat lymphocytes but increased the formation of lactate and aspartate. 6. In contrast, propionate inhibited by 50% the synthesis of lymphocyte lipid from [1-14C]acetate at concentrations of 0.5 and 1 mmol/l and reduced by half the incorporation of 3H2O into lipids at 1 and 5 mmol/l. 7. The results suggest that inhibition of lipid synthesis is a possible mechanism leading to reduction of lymphocytes proliferation.

Adult↗
PubMed1993

The effects of fatty acids on lymphocyte functions.

1. Lymphocytes play an important role in cell-mediated immunity and have been implicated in inflammatory and autoimmune diseases. 2. Unsaturated fatty acids, including oleic, linoleic, alpha-linolenic, arachidonic, eicosapentaenoic and docosahexaenoic acids, inhibit mitogen-stimulated lymphocyte proliferation in vitro. The inhibition of proliferation is dependent upon the concentration of fatty acid, the time during culture of fatty acid addition, the duration of exposure of the cells to the fatty acid and the chain length and degree of unsaturation of the fatty acid. 3. Unsaturated fatty acids suppress production of the immunoregulatory cytokine interleukin-2 by lymphocytes in vitro. 4. Triacylglycerols containing unsaturated fatty acids inhibit lymphocyte proliferation and natural killer cell activity in vitro. 5. Feeding weanling rats diets containing olive oil, evening primrose oil or fish oil results in suppression of lymphocyte proliferation. 6. Preliminary studies indicated that supplementation of the diet of healthy humans with fish oil-containing capsules suppresses lymphocyte proliferation and interleukin-2 production. 7. These effects, along with inhibitory effects upon the functions of other cells involved in the immune response, in particular monocytes and macrophages, indicate that certain unsaturated fatty acid-containing oils (particularly evening primrose oil and fish oil) may be of benefit in the treatment of inflammatory and autoimmune diseases.

Animals↗
PubMed1993

Influence of antioxidant vitamins on fatty acid inhibition of lymphocyte proliferation.

Fatty acids, especially polyunsaturated fatty acids (PUFAs), inhibit a number of lymphocyte functions, including proliferation, cytokine production and cytotoxicity, but their mechanism of action is not known. This study investigated whether fatty acids inhibit lymphocyte proliferation by leading to the production of lipid peroxides, which are known to inhibit the growth of cells. The so-called "thiobarbituric acid-reactive substances" (TBARS) and lipid hydroperoxide contents of lymphocytes (0.75 +/- 0.04 and 1.30 +/- 0.39 nmol/mg protein in fresh cells, respectively) were increased by 48 h culture to 0.96 +/- 0.14 and 3.23 +/- 0.47 nmol/mg protein, respectively. The TBARS content was increased by culture in the presence of 100 microM PUFAs to between 1.46 +/- 0.11 (linoleic acid) and 2.39 +/- 0.31 (docosahexaenoic acid) nmol/mg protein. The lipid hydroperoxide content was increased by culture in the presence of 100 microM PUFAs to between 11.65 +/- 1.12 (linoleic acid) and 22.24 +/- 1.26 (docosahexaenoic acid) nmol/mg protein. These increases were partially prevented by inclusion of 10 microM vitamin E in the culture medium. Vitamin E (1 or 10 microM) enhanced concanavalin A-stimulated rat lymphocyte proliferation by approximately 45%. Vitamin E (10 microM) increased human lymphocyte proliferation by 35%. However, vitamin E did not prevent the inhibitory effects of fatty acids upon lymphocyte proliferation. It is concluded that inhibition of lymphocyte proliferation by fatty acids is not caused by their conversion to peroxidised products.

Animals↗
PubMed1992

Site-specific differences in the fatty acid composition of human adipose tissue.

The fatty acid composition of triacylglycerols from fifteen distinct adipose depots taken from each of seven adult male human subjects was compared. Oleic, palmitic, linoleic, stearic, myristic, palmitoleic and vaccenic acids accounted for more than 90% of the triacylglycerol fatty acids in all sites from all subjects; a number of other fatty acids were also identified and quantified. There were large differences in the average fatty acid composition between individual subjects. There were no site-specific differences in the proportions of myristic (3.8-4.7% of triacylglycerol fatty acids), palmitic (23-29%), linoleic (6.7-9.8%) or vaccenic (4.1-4.7%) acids or in the proportions of any of the less abundant fatty acids. There were some significant site-specific differences in the proportions of palmitoleic, oleic and stearic acids. The calf depot contained more palmitoleic acid (6.41 +/- 1.09%) than the trapezius (3.12 +/- 0.55%), perirenal (3.59 +/- 0.50%) and mesenteric (3.70 +/- 0.43%) depots, more oleic acid (42.13 +/- 1.27%) than the trapezius (36.03 +/- 2.18%), perirenal (36.50 +/- 1.56%) and breast (37.13 +/- 1.55%) depots and less stearic acid (5.18 +/- 0.89%) than the trapezius (8.57 +/- 0.97%), perirenal (8.49 +/- 0.75%), mesenteric (7.87 +/- 0.42%), breast (8.02 +/- 0.75%) and clavicular (8.34 +/- 0.78%) depots. The buttock depot contained less stearic acid (6.06 +/- 0.65%) than the perirenal, mesenteric and clavicular depots, while the anterior thigh depot contained less stearic acid (6.07 +/- 0.70%) than the perirenal depot. These findings indicate that, while most human adipose depots differ little in fatty acid composition, some sites, in particular the calf, perirenal, trapezius and mesenteric depots, have site-specific properties.

Adipose Tissue↗
PubMed1992

Heterogeneity of glycogen synthesis upon refeeding following starvation.

1. Starvation of rats for 40 hr decreased the body weight, liver weight and blood glucose concentration. The hepatic and skeletal muscle glycogen concentrations were decreased by 95% (from 410 mumol/g tissue to 16 mumol/g tissue) and 55% (from 40 mumol/g tissue to 18.5 mumol/g tissue), respectively. 2. Fine structural analysis of glycogen purified from the liver and skeletal muscle of starved rats suggested that the glycogenolysis included a lysosomal component, in addition to the conventional phosphorolytic pathway. In support of this the hepatic acid alpha-glucosidase activity increased 1.8-fold following starvation. 3. Refeeding resulted in liver glycogen synthesis at a linear rate of 40 mumol/g tissue per hr over the first 13 hr of refeeding. The hepatic glycogen store were replenished by 8 hr of refeeding, but synthesis continued and the hepatic glycogen content peaked at 24 hr (approximately 670 mumol/g tissue). 4. Refeeding resulted in skeletal muscle glycogen synthesis at an initial rate of 40 mumol/g tissue per hr. The muscle glycogen store was replenished by 30 min of refeeding, but synthesis continued and the glycogen content peaked at 13 hr (approximately 50 mumol/g tissue). 5. Both liver and skeletal muscle glycogen synthesis were inhomogeneous with respect to molecular size; high molecular weight glycogen was initially synthesised at a faster rate than low molecular weight glycogen. These observations support suggestions that there is more than a single site of glycogen synthesis.

Animals↗
PubMed1992

Polyunsaturated fatty acids suppress human peripheral blood lymphocyte proliferation and interleukin-2 production.

1. The effects of a variety of fatty acids on human peripheral blood lymphocyte proliferation stimulated by concanavalin A or purified protein derivative of Mycobacterium tuberculosis were studied. 2. The proliferative response to concanavalin A was inhibited by all of the polyunsaturated fatty acids tested (eicosapentaenoate, arachidonate, docosahexaenoate, linoleate and alpha-linolenate) and also by the saturated fatty acid, stearate. The greatest inhibition of proliferation (approximately 85%) was caused by eicosapentaenoate. 3. The proliferative response to the purified protein derivative of Mycobacterium tuberculosis was inhibited by all of the polyunsaturated fatty acids tested, except alpha-linolenate, and also by stearate. The greatest inhibition of proliferation (approximately 75%) was caused by eicosapentaenoate. 4. The pattern of inhibition of proliferation by fatty acids was similar to that previously reported for rat lymphocytes with one exception: oleate did not inhibit human lymphocyte proliferation. 5. The proliferation of T-lymphocytes is dependent upon their ability to synthesize and secrete the cytokine, interleukin-2. In the presence of mitogen the concentration of interleukin-2 in the culture medium increased markedly above that in the medium of non-stimulated cells. 6. All polyunsaturated fatty acids tested caused a decrease in the concentration of interleukin-2; the greatest decrease (approximately 90%) was caused by eicosapentaenoate. 7. There was a good correlation between lymphocyte proliferation in the presence of fatty acids and interleukin-2 concentration. However, stearate did not decrease the interleukin-2 concentration but did inhibit lymphocyte proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Plasma amino acid concentrations in the overtraining syndrome: possible effects on the immune system.

Overtraining and long-term exercise are associated with an impairment of immune function. We provide evidence in support of the hypothesis that the supply of glutamine, a key fuel for cells of the immune system, is impaired in these conditions and that this may contribute to immunosuppression. Plasma glutamine concentration was decreased in overtrained athletes and after long-term exercise (marathon race) and was increased after short-term, high intensity exercise (sprinting). Branched chain amino acid supplementation during long-term exercise was shown to prevent this decrease in the plasma glutamine level. Overtraining was without effect on the rate of T-lymphocyte proliferation in vitro or on the plasma levels of interleukin-1 and -6, suggesting that immune function is not impaired in this condition. Given the proposed importance of glutamine for cells of the immune system, it is concluded that the decrease in plasma glutamine concentration in overtraining and following long-term exercise, and not an intrinsic defect in T lymphocyte function, may contribute to the immune deficiency reported in these conditions.

Adult↗
PubMed1992

The inhibition of T-lymphocyte proliferation by fatty acids is via an eicosanoid-independent mechanism.

Eicosanoids, in particular prostaglandin E2 (PGE2), are potent inhibitors of a number of immune responses, including lymphocyte proliferation. We have previously shown that fatty acids, especially polyunsaturated fatty acids (PUFA), inhibit mitogen-stimulated proliferation of lymphocytes. One mechanism by which fatty acids could exert their inhibitory effect is via modulation of eicosanoid synthesis. This possibility was investigated in the present study. PGE2 concentrations in the medium taken from lymphocytes cultured in the presence of a range of different fatty acids did not correlate with the inhibitory effects of the fatty acids upon lymphocyte proliferation. Although PGE2 at concentrations above 10 nM caused inhibition of lymphocyte proliferation, PGE2 at the concentration measured in lymphocyte culture medium (0.3-4 nM) was not inhibitory. PGE3 did not inhibit lymphocyte proliferation, except at high concentrations (greater than 250 nM). The maximal inhibition of proliferation caused by PGE2 or PGE3 was less than the inhibition caused by each of the fatty acids except myristic or palmitic acids. Inclusion of inhibitors of phospholipase A2, cyclo-oxygenase or lipoxygenase in the culture medium did not prevent the fatty acids from exerting their inhibitory effect on lymphocyte proliferation. The eicosanoids present in lymph node cell cultures originate from macrophages rather than lymphocytes. Depletion of macrophages from the cell preparation by adherence did not prevent fatty acids from inhibiting proliferation. Proliferation of thoracic duct lymphocytes, which are devoid of macrophages, is inhibited by fatty acids to a similar extent as proliferation of lymph node lymphocytes. These observations provide convincing evidence that the inhibition of lymphocyte proliferation by fatty acids is independent of the production of eicosanoids. Therefore, other mechanisms must be investigated if the effect of fatty acids upon lymphocyte proliferation is to be understood at a biochemical level.

Alprostadil↗
PubMed1991

Effect of fatty acids on the proliferation of concanavalin A-stimulated rat lymph node lymphocytes.

1. The effect of a range of fatty acids upon concanavalin A-stimulated [3H]thymidine incorporation into rat lymphocytes was investigated. 2. All fatty acids tested inhibited the response to mitogen but the extent of the inhibition was dependent upon the fatty acid concentration used, the time of addition of fatty acid and the duration of exposure of the cells to fatty acid. 3. All fatty acids were inhibitory at concentrations of 50 microM or above; at lower concentrations some were inhibitory and some were stimulatory. Above 50 microM the inhibitory effect was concentration dependent; the greater the fatty acid concentration, the greater the inhibition. 4. The longer the lymphocytes were exposed to the fatty acid the greater was the inhibitory effect. This was true if the fatty acids were added at the same time as the mitogenic stimulus or if they were added before or after the stimulus. Some fatty acids maintained their inhibitory effect when added 24 or 48 hr after the mitogenic stimulus. 5. Generally unsaturated fatty acids were more inhibitory than saturated fatty acids; the greatest inhibition of proliferation was caused by eicosapentaenoate and arachidonate and the least inhibition by myristate and palmitate. 6. Inhibition was greater in the absence of serum. 7. Inhibition by unsaturated fatty acids could be partially or totally relieved by addition in combination with myristate or palmitate, suggesting that the inhibitory effect of fatty acids may be due to alteration of membrane fluidity caused by an imbalance of fatty acids presented to the cells. 8. PGE2 levels were similar in the medium of cells grown in the presence of fatty acids with varying inhibitory effects, indicating that PGE2 production is not the sole mechanism of suppression of the proliferative response. 9. Although the mechanism by which fatty acids exert their effect remains to be determined, these results indicate that lymphocyte proliferation and so an immune response could be influenced by dietary lipid manipulation.

Animals↗
PubMed1990

Does glutamine contribute to immunosuppression after major burns?

The effects of glutamine concentration on the rates of lymphocyte proliferation after mitogenic stimulation and of phagocytosis by macrophages were investigated in vitro. A decrease in the glutamine concentration in culture medium from 0.6 to 0.05 mmol/l greatly decreased the rate of proliferation of human lymphocytes and of phagocytosis by mouse macrophages. In patients with major burn injury plasma glutamine concentration was 58% lower than that in normal controls and it remained low for at least 21 days after the injury. The findings indicate that the decrease in plasma glutamine concentration may contribute to the injury-induced impairment of immune function occurring after major burn injury.

Adult↗
PubMed1990

Uptake and incorporation of saturated and unsaturated fatty acids into macrophage lipids and their effect upon macrophage adhesion and phagocytosis.

Murine thioglycollate-elicited peritoneal macrophages were cultured in the presence of a variety of fatty acids added as complexes with bovine serum albumin. All fatty acids tested were taken up readily by the cells and both neutral and phospholipid fractions were enriched with the fatty acid provided in the medium. This generated a range of cells enriched in saturated, monounsaturated or polyunsaturated fatty acids, including n-3 acids of fish oil origin. Saturated fatty acid enrichment enhanced macrophage adhesion to both tissue culture plastic and bacterial plastic compared with enrichment with polyunsaturated fatty acids. Macrophages enriched with the saturated fatty acids myristate or palmitate showed decreases of 28% and 21% respectively in their ability to phagocytose unopsonized zymosan particles. Those enriched with polyunsaturated fatty acids showed 25-55% enhancement of phagocytic capacity. The greatest rate of uptake was with arachidonate-enriched cells. Phagocytic rate was highly correlated with the saturated/unsaturated fatty acid ratio, percentage of polyunsaturated fatty acid and index of unsaturation, except for macrophages enriched with fish-oil-derived fatty acids; they showed lower phagocytic activity than expected on the basis of their degree of unsaturation. These results suggest that membrane fluidity is important in determining macrophage adhesion and phagocytic activity. However, in the case of phagocytosis, this effect may be partially overcome if the cells are enriched with fish-oil-derived fatty acids. Thus it may be possible to modulate the activity of cells of the immune system, and so an immune response, by dietary lipid manipulation.

Animals↗