Enhanced metabolism of glucose and glutamine in mesenteric lymph node lymphocytes from spontaneously diabetic BB rats

1994 ◽  
Vol 72 (7) ◽  
pp. 827-832 ◽  
Author(s):  
Catherine J. Field ◽  
Guoyao Wu ◽  
Errol B. Marliss

Increased energy substrate metabolism accompanies the functional activation of extrathymic immunocytes in the autoimmune BB diabetic rat, but the specific cells responsible have not been identified. To determine the possible contribution of lymphocytes to the elevated metabolism of glucose and glutamine, mesenteric lymph node cells were selected because they contain few macrophages or natural killer (NK) cells. Results from diabetic (BBd, n = 7) and non-diabetes-prone (BBn, n = 7) rats were compared with those from streptozotocin-induced diabetic (STZ-BBn, n = 6) rats. In BBd cells, all measured metabolites of glutamine (CO2, glutamate, aspartate, and NH3) in the presence of 5 mM glucose were elevated (1.5- to 2.5-fold) compared with BBn. In contrast, the only product of glucose metabolism (in the presence of 2 mM glutamine) that was increased was pyruvate (1.6-fold). All measured products of glucose metabolism were significantly lower in cells from STZ-BBn than from BBn rats. Products from glutamine did not differ. Calculated potential ATP production was greater (p < 0.05) in BBd than in BBn and STZ-BBn cells (86 ± 5 vs. 65 ± 2 and 53 ± 5 nmol∙2 h−1∙10−6 cells, respectively). However, in BBn and STZ-BBn rats, about three quarters of the cells were T (CD5+) cells and one quarter were B (MARK-1+) cells, whereas in BBd three quarters of the cells were MARK-1+. Therefore, to distinguish the role of T- versus B-cells, enriched T-lymphocyte (CD5+) preparations were studied: glutamate (5.3-fold) and NH3 (4.2-fold) production from glutamine and lactate (1.7-fold) production from glucose were greater (p < 0.05) in cells from BBd rats. This establishes that in BBd cells (i) lymphocytes (especially CD4+) contribute to the increased metabolism, (ii) T-lymphocytes are especially active in glutamine metabolism, but because of their reduced numbers, this cannot fully account for the increase in the unfractionated population, and therefore (iii) B-lymphocytes probably also contribute, and (iv) the altered metabolism of these cells is not a result of the diabetic state. These findings are consistent with activation of immunocytes of multiple lineages in this autoimmune syndrome.Key words: glutamine, glucose, lymphocytes, BB rat.

1991 ◽  
Vol 260 (1) ◽  
pp. E141-E147 ◽  
Author(s):  
G. Y. Wu ◽  
C. J. Field ◽  
E. B. Marliss

The metabolism of glutamine (2 mM) and glucose (5 mM) was studied in splenocytes and mesenteric lymph node lymphocytes of Wistar-Furth rats to assess their relative importance as energy substrates. The major products from glutamine were ammonia, glutamate, aspartate, and CO2, whereas those from glucose were lactate, pyruvate, and CO2 in cells from both lymphoid organs. The individual rates of glutamine and glucose metabolism were decreased in the presence of both substrates, compared with the rates when present separately. The rates of glucose and some (but not all) aspects of glutamine metabolism were higher (P less than 0.01) in splenocytes than in mesenteric lymphocytes. In cells from both lymphoid organs, glutamine and glucose could potentially contribute almost equal amounts of ATP in the presence of both substrates. Glutamine and glucose individually were able to provide sufficient amounts of ATP to maintain its concentrations in the cells throughout a 2-h incubation period at the same levels as with both substrates present. We also found that splenocyte concentration (3.3-100 x 10(6) cells/ml) in the incubations is an important determinant of rates of metabolite formation from glutamine when expressed per 10(6) cells. We conclude that glucose is not the only quantitatively significant energy substrate or even the major one for lymphocytes, because glutamine at near-physiological concentration can be readily utilized by these cells.


Parasitology ◽  
1977 ◽  
Vol 74 (3) ◽  
pp. 225-234 ◽  
Author(s):  
D. Wakelin ◽  
Margaret M. Wilson

When mice were irradiated immediately before infection withTrichinella spiralisthere was a profound and long-lasting interference with their ability to expel adult worms from the intestine. Irradiation given after the fifth day of infection was progressively less effective in this respect. The ability to expel worms was not restored when mesenteric lymph node cells (MLNC) were transferred (a) on the day of infection in mice irradiated one day previously, or (b) on day 7 of an infection in mice irradiated on day 6, even though the MLNC transferred immunity to intact recipients. Transfer of bone marrow (BM) alone was also without effect. However, worm explusion was restored if, following irradiation and injection of BM, 10 days were allowed for BM differentiation before transfer of MLNC. This restoration was effective even after lethal levels of irradiation and was clearly dependent upon a donor-derived BM component cooperating with, or responding to, the activity of the transferred MLNC. The possibility that the BM component is non-lymphoid in nature is discussed.


Metabolism ◽  
2000 ◽  
Vol 49 (9) ◽  
pp. 1111-1117 ◽  
Author(s):  
Fraser W. Scott ◽  
Elizabeth Olivares ◽  
Abdullah Sener ◽  
Willy J. Malaisse

1991 ◽  
Vol 274 (1) ◽  
pp. 49-54 ◽  
Author(s):  
G Wu ◽  
C J Field ◽  
E B Marliss

To investigate the metabolic fates of glutamine in splenocytes from the BB rat with spontaneous immunologically mediated insulin-dependent diabetes, freshly isolated cells were incubated in Krebs-Ringer Hepes buffer with 1.0 mM-[U-14C]glutamine and 0, 4 mM- or 15 mM-glucose. (1) The major products of glutamine metabolism in splenocytes from normal and diabetic rats were ammonia, glutamate, aspartate and CO2. (2) The addition of glucose increased (P less than 0.01) glutamate production, but decreased (P less than 0.01) aspartate and CO2 production from glutamine, as compared with the values obtained in the absence of glucose. However, there were no differences in these metabolites of glutamine at 4 mM- and 15 mM-glucose. (3) At all glucose concentrations used, the productions of ammonia, glutamate, aspartate and CO2 from glutamine were all markedly increased (P less than 0.01) in splenocytes from diabetic rats. (4) Potential ATP production from glutamine in the splenocytes was similar to that from glucose, and was increased in cells from the diabetic rat. (5) ATP concentrations were increased (P less than 0.01) in diabetic-rat splenocytes in the presence of glutamine with or without glucose. (6) Our results demonstrate that glutamine is an important energy substrate for splenocytes and suggest that the increased glutamine metabolism may be associated with the activation of certain subsets of splenocytes in the immunologically mediated diabetic syndrome.


2006 ◽  
Vol 143 (3) ◽  
pp. 474-483 ◽  
Author(s):  
F. Hoentjen ◽  
S. L. Tonkonogy ◽  
B. Liu ◽  
R. B. Sartor ◽  
J. D. Taurog ◽  
...  

Parasitology ◽  
1982 ◽  
Vol 84 (2) ◽  
pp. 381-389 ◽  
Author(s):  
T. D. G. Lee ◽  
R. K. Grencis ◽  
D. Wakelin

SUMMARYInfections with either 300 infective Trichinella spiralis larvae or 400 embryonated eggs of Trichuris muris were effective in eliciting accelerated expulsion of heterologous challenge infections given 20 days after the primary infection. Accelerated expulsion could also be achieved by the administration of soluble crude worm antigen given 12 days prior to heterologous challenge or by adoptive transfer of mesenteric lymph node cells taken from mice infected with the heterologous parasite. Each species is capable of eliciting an accelerated secondary expulsion response in hosts that have been actively or adoptively immunized against the other species and these results are taken to indicate that there is a specific cross-immunity between T. spiralis and T. muris due to shared antigens. It is postulated that these shared antigens are derived from stichocyte granules.


Parasitology ◽  
1976 ◽  
Vol 72 (3) ◽  
pp. 307-315 ◽  
Author(s):  
D. Wakelin ◽  
M. Lloyd

SummaryImmunity to the adult stage of Trichinella spiralis, assessed by an acceleration of worm expulsion, was transferred to recipient mice with mesenteric lymph node cells (MLNC) or serum taken from infected donors. Immunity was transferred most effectively by MLNC taken from donors infected for 8 days, i.e. donors actively responding to infection. Transfer of both MLNC and serum brought about a marked acceleration of worm expulsion in all cases, even where MLNC or serum given separately failed to transfer a significant degree of immunity.


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