Plasma Glutamate Concentration and Lymphocyte Activity

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 1988 Jan 1

PMID 2895110

Citations 14

Authors

W Droge

H P Eck

M Betzler

P Schlag

P Drings

W Ebert

Affiliations

Soon will be listed here.

Abstract

Elevated glutamate concentrations are commonly observed in tumor patients, and glutamate was recently found to competitively inhibit the membrane transport of cystine. We therefore investigated the possibility that elevated plasma glutamate levels may damage the immune system. The experiments in this report demonstrate a link between the individual plasma glutamate level and the individual immunological reactivity as measured by mitogenic responses. This correlation has been analyzed in 39 colorectal carcinoma patients, 40 oat cell carcinoma patients, 24 large cell lung carcinoma patients, and 31 apparently healthy persons (blood donors). Blood cells from all three groups of tumor patients in comparison with cells from healthy persons produced markedly reduced mitogenic responses against PWM, and all three groups of tumor patients had on average significantly elevated plasma glutamic acid concentrations. Our analysis revealed a linear regression of the logarithm of the individual plasma glutamate levels (before therapeutic treatment) on the logarithm of the corresponding mitogenic reactivity against PWM for the entire population of 134 persons tested (correlation coefficient -0.80; level of significance P less than 0.00001). A statistically significant linear correlation with a similar regression equation was also observed in the group of the healthy blood donors (n = 31; correlation coefficient -0.56; P less than 0.01), indicating that this correlation is universal and not dependent on the presence of a tumor. Mitogenically stimulated murine lymphocyte cultures revealed an inverse correlation between glutamate concentration and cell proliferation in response to the mitogens PHA and PWM.

Citing Articles

Metabolome-wide association study on physical activity.

Kojouri M, Pinto R, Mustafa R, Huang J, Gao H, Elliott P Sci Rep. 2023; 13(1):2374.

PMID: 36759570 PMC: 9911764. DOI: 10.1038/s41598-022-26377-7.

Glutamatergic system components as potential biomarkers and therapeutic targets in cancer in non-neural organs.

Garcia-Gaytan A, Hernandez-Abrego A, Diaz-Munoz M, Mendez I Front Endocrinol (Lausanne). 2022; 13:1029210.

PMID: 36457557 PMC: 9705578. DOI: 10.3389/fendo.2022.1029210.

Severe COVID-19 Is Characterised by Perturbations in Plasma Amines Correlated with Immune Response Markers, and Linked to Inflammation and Oxidative Stress.

Karu N, Kindt A, van Gammeren A, Ermens A, Harms A, Portengen L Metabolites. 2022; 12(7).

PMID: 35888742 PMC: 9321395. DOI: 10.3390/metabo12070618.

The Cancer Immunogram as a Framework for Personalized Immunotherapy in Urothelial Cancer.

van Dijk N, Funt S, Blank C, Powles T, Rosenberg J, van der Heijden M Eur Urol. 2018; 75(3):435-444.

PMID: 30274701 PMC: 6697269. DOI: 10.1016/j.eururo.2018.09.022.

Metabolic Hallmarks of Tumor and Immune Cells in the Tumor Microenvironment.

Renner K, Singer K, Koehl G, Geissler E, Peter K, Siska P Front Immunol. 2017; 8:248.

PMID: 28337200 PMC: 5340776. DOI: 10.3389/fimmu.2017.00248.

References

de Jong B, Van der Meer I . Augmentation of Chinese hamster lymphocyte stimulation by cysteine. J Immunol Methods. 1984; 68(1-2):55-60. DOI: 10.1016/0022-1759(84)90136-4. View

Vose B, Vanky F, Klein E . Human tumour--lymphocyte interaction in vitro. V. Comparison of the reactivity of tumour-infiltrating, blood and lymph-node lymphocytes with autologous tumour cells. Int J Cancer. 1977; 20(6):895-902. DOI: 10.1002/ijc.2910200612. View

Muller D, Manger B, Zawatzky R, Kirchner H, Kalden J . Mitogen-induced gamma interferon production in peripheral blood lymphocytes from patients with colorectal tumors. Immunobiology. 1984; 166(4-5):494-9. DOI: 10.1016/s0171-2985(84)80026-1. View

Bannai S . Exchange of cystine and glutamate across plasma membrane of human fibroblasts. J Biol Chem. 1986; 261(5):2256-63. View

Braun D, Cobleigh M, Harris J . Multiple concurrent immunoregulatory defects in cancer patients with depressed PHA-induced lymphocyte DNA synthesis. Clin Immunol Immunopathol. 1980; 17(1):89-101. DOI: 10.1016/0090-1229(80)90076-8. View

Leroux M, Schindler L, Braun R, Doerr H, Geisen H, Kirchner H . A whole-blood lymphoproliferation assay for measuring cellular immunity against herpes viruses. J Immunol Methods. 1985; 79(2):251-62. DOI: 10.1016/0022-1759(85)90105-x. View

Beaton J, McGANITY W, McHenry E . Plasma glutamic acid levels in malignancy. Can Med Assoc J. 1951; 65(3):219-21. PMC: 1822071. View

Watanabe H, Bannai S . Induction of cystine transport activity in mouse peritoneal macrophages. J Exp Med. 1987; 165(3):628-40. PMC: 2188288. DOI: 10.1084/jem.165.3.628. View

Collins P, Johnson A, Moriarty M . T-lymphocytes in human cancer. I. Mitogen-responsiveness of lymphocytes in cancer patients. Ir J Med Sci. 1980; 149(8):301-6. DOI: 10.1007/BF02939160. View

10.

Totterman T, Parthenais E, Hayry P, Timonen T, Saksela E . Cytological and functional analysis of inflammatory infiltrates in human malignant tumors. III. Further functional investigations using cultured autochthonous tumor cell lines and freeze-thawed infiltrating inflammatory cells. Cell Immunol. 1980; 55(1):219-26. DOI: 10.1016/0008-8749(80)90153-7. View

11.

Ohmori H, Yamamoto I . Mechanism of augmentation of the antibody response in vitro by 2-mercaptoethanol in murine lymphocytes. I. 2-Mercaptoethanol-induced stimulation of the uptake of cystine, an essential amino acid. J Exp Med. 1982; 155(5):1277-90. PMC: 2186673. DOI: 10.1084/jem.155.5.1277. View

12.

Wanebo H, Jun M, Strong E, Oettgen H . T-cell deficiency in patients with squamous cell cancer of the head and neck. Am J Surg. 1975; 130(4):445-51. DOI: 10.1016/0002-9610(75)90482-1. View

13.

Miescher S, Whiteside T, Carrel S, Von Fliedner V . Functional properties of tumor-infiltrating and blood lymphocytes in patients with solid tumors: effects of tumor cells and their supernatants on proliferative responses of lymphocytes. J Immunol. 1986; 136(5):1899-907. View

14.

BALLANTYNE R, McHenry E . Vitamin B6 and biotin in human cancer tissue. Cancer Res. 1949; 9(11):689-91. View

15.

White J, Beaton J, McHenry E . Observations on plasma glutamic acid. J Lab Clin Med. 1952; 40(5):703-6. View

16.

White J, OZAWA G, Ross G, McHenry E . An effect of neoplasms on glutamic acid metabolism in the host. Cancer Res. 1954; 14(7):508-12. View

17.

Watkins S . The effects of surgery on lymphocyte transformation in patients with cancer. Clin Exp Immunol. 1973; 14(1):69-76. PMC: 1553846. View

18.

Yron I, Schickler M, Fisch B, Pinkas H, Ovadia J, Witz I . The immune system during the pre-cancer and the early cancer period. IL-2 production by PBL from post-menopausal women with and without endometrial carcinoma. Int J Cancer. 1986; 38(3):331-8. DOI: 10.1002/ijc.2910380306. View

19.

Wu C, Bauer J . A study of free amino acids and of glutamine synthesis in tumor-bearing rats. Cancer Res. 1960; 20:848-57. View

20.

Makowske M, CHRISTENSEN H . Contrasts in transport systems for anionic amino acids in hepatocytes and a hepatoma cell line HTC. J Biol Chem. 1982; 257(10):5663-70. View