Spittler A, Winkler S, Götzinger P, Oehler R, Willheim M, Tempfer C, Weigel G, Függer R, Boltz-Nitulescu G, Roth E
Department of Surgery, University of Vienna, Austria.
Blood. 1995 Aug 15;86(4):1564-9.
Reduced concentrations of glutamine (GLN) in plasma and skeletal muscle, defective host defense systems, and a diminished expression of the HLA-DR antigen on monocytes are important diagnostic parameters for late post-injury sepsis. In this in vitro study, we investigated whether blood monocyte-derived macrophage antigen expression and function from healthy donors is influenced by GLN. Lowering the GLN concentration in culture medium from 2 mmol/L to 200 mumol/L reduced the expression of HLA-DR by 40% (P < .001) on monocyte-derived macrophages, and decreased tetanus toxoid-induced antigen presentation. In addition, low GLN levels downregulated the expression of intercellular adhesion molecule-1 (ICAM-1/CD54), Fc receptor for IgG (Fc gamma RI/CD64), and complement receptors type 3 (CR3; CD11b/CD18) and type 4 (CR4; CD11c/CD18). A correlation was found between the phagocytosis of IgG-sensitized ox erythrocytes or opsonized Escherichia coli and the decreased expression of Fc gamma RI and CR3. Monocyte expression of CD14, CD71, and Fc gamma RIII/CD16 and capacity to phagocytose latex beads were not affected by altering the level of GLN. Depletion of GLN was associated with a significant reduction in cellular adenosine triphosphate (ATP), which may have influenced cell surface marker expression and phagocytosis. It remains to be seen whether these in vitro findings are of clinical significance in the treatment of sepsis.
血浆和骨骼肌中谷氨酰胺(GLN)浓度降低、宿主防御系统缺陷以及单核细胞上HLA - DR抗原表达减少是损伤后晚期脓毒症的重要诊断参数。在这项体外研究中,我们调查了来自健康供体的血液单核细胞衍生巨噬细胞的抗原表达和功能是否受谷氨酰胺影响。将培养基中谷氨酰胺浓度从2 mmol/L降至200 μmol/L,可使单核细胞衍生巨噬细胞上HLA - DR的表达降低40%(P <.001),并减少破伤风类毒素诱导的抗原呈递。此外,低谷氨酰胺水平下调细胞间黏附分子 - 1(ICAM - 1/CD54)、IgG的Fc受体(FcγRI/CD64)以及3型补体受体(CR3;CD11b/CD18)和4型补体受体(CR4;CD11c/CD18)的表达。发现IgG致敏的牛红细胞或调理的大肠杆菌的吞噬作用与FcγRI和CR3表达降低之间存在相关性。改变谷氨酰胺水平未影响CD14、CD71和FcγRIII/CD16的单核细胞表达以及吞噬乳胶珠的能力。谷氨酰胺耗竭与细胞三磷酸腺苷(ATP)显著减少有关,这可能影响了细胞表面标志物表达和吞噬作用。这些体外研究结果在脓毒症治疗中是否具有临床意义还有待观察。