Abstract
Elevated glutamate concentrations are commonly observed in patients with advanced carcinoma, and glutamate was recently found to inhibit the membrane transport of cystine and to impair the function of macrophages and lymphocytes in vitro. We therefore investigated the possibility that elevated plasma glutamate levels may be quantitatively correlated with reduced lymphocyte reactivity and an impaired host response to the tumor. Here we report the results of a study on patients with bronchial carcinoma, which show that patients with plasma glutamate levels above 120 μM have a lower lymphocyte response to mitogens and a substantially higher death rate than those with glutamate levels below 120 μM. This correlation does not prove a causal role of glutamate, but it confirms predictions from the in vitro laboratory data.
Key words: Plasma glutamate levels, Lymphocyte reactivity, Death rate, Bronchial carcinoma
References
- Chawla RK, Lewis FW, Kutner MH, Bate DM, Roy RGB, Rudman D (1984) Plasma cysteine, cystine, and glutathione in cirrhosis. Gastroenterology 87:770–776 [PubMed] [Google Scholar]
- De Vries JE, Caviles AP, Bont WS, Mendelsohn J (1979) The role of monocytes in human lymphocyte activation by mitogens. J Immunol 122:1099–1107 [PubMed] [Google Scholar]
- Dröge W, Eck H-P, Näher H, Pekar U, Daniel V (1988a) Abnormal amino-acid concentrations in blood of patients with acquired immunodeficiency syndrome (AIDS) may contribute to the immunological defect. Biol Chem Hoppe Seyler 369:143–148 [DOI] [PubMed] [Google Scholar]
- Dröge W, Eck H-P, Betzler M, Schlag P, Drings P, Ebert W (1988b) Plasma glutamate concentration and lymphocyte activity. J Cancer Res Clin Oncol 114:124–128 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eck H-P, Dröge W (1989) Influence of the extracellular glutamate concentration on the intracellular cyst(e)ine concentration in macrophages and on the capacity to release cysteine. Biol Chem Hoppe Seyler 370:109–113 [DOI] [PubMed] [Google Scholar]
- Eck H-P, Gmünder H, Hartmann M, Petzoldt D, Daniel V, Dröge W (1989) Low concentrations of acid-soluble thiol (cysteine) in the blood plasma of HIV-1 infected patients. Biol Chem Hoppe Seyler 370:101–108 [DOI] [PubMed] [Google Scholar]
- Leroux M, Schindler L, Braun R, Doerr HW, Geisen HW, Kirchner H (1985) A whole-blood lymphoproliferation assay for measuring cellular immunity against herpes viruses. J Immunol Methods 79:251–262 [DOI] [PubMed] [Google Scholar]
- Manke H-G, Aulenbacher P (1985) Veränderungen des Immunsystems bei Patienten mit Bronchialkarzinom. In: Drings P, Schmähl D, Vogt-Moykopf I (eds) Aktuelle Onkologie 26; Bronchialkarzinom. W. Zuckschwerdt, München, p 194 [Google Scholar]
- Miedema F, Petit AJC, Terpstra FG, Schattenkerk JKME, De Wolf F, Al BJM, Roos M, Lange JMA, Dammer SA, Gondsmit J; Schellekens PTA (1988) Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men. J Clin Invest 82:1908–1914 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenthal AS (1978) Determinant selection and macrophages function in genetic control of the immune response. Immunol Rev 40:136–152 [DOI] [PubMed] [Google Scholar]
- Rosenstreich DL, Farrar JJ, Dougherty S (1976) Absolute macrophage dependency of T lymphocyte activation by mitogens. J Immunol 116:131–139 [PubMed] [Google Scholar]
- Saetre R, Rabenstein DL (1978) Determination of cysteine in plasma and urine and homocysteine in plasma by high-pressure liquid chromatography. Anal Biochem 90:684–692 [DOI] [PubMed] [Google Scholar]
- Schwab R, Crow MK, Russo C, Weksler ME (1985) Requirements for T cell activation by OKT3 monoclonal antibody: role of modulation of T3 molecules and interleukin 1. J Immunol 135:1714–1718 [PubMed] [Google Scholar]
- Thiele DL, Lipsky PE (1982) The accessory function of phagocytic cells in human T cell and B cell responses. J Immunol 129:1033–1040 [PubMed] [Google Scholar]
- Watanabe H, Bannai S (1987) Induction of cysteine transport activity in mouse peritoneal macrophages. J Exp Med 165:628–640 [DOI] [PMC free article] [PubMed] [Google Scholar]