Calder P C, Bevan S J, Newsholme E A
Department of Biochemistry, University of Oxford, U.K.
Immunology. 1992 Jan;75(1):108-15.
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.
类花生酸，尤其是前列腺素E2（PGE2），是多种免疫反应的强效抑制剂，包括淋巴细胞增殖。我们之前已经表明，脂肪酸，尤其是多不饱和脂肪酸（PUFA），可抑制丝裂原刺激的淋巴细胞增殖。脂肪酸发挥其抑制作用的一种机制可能是通过调节类花生酸的合成。本研究对这一可能性进行了调查。在一系列不同脂肪酸存在下培养的淋巴细胞培养基中，PGE2的浓度与脂肪酸对淋巴细胞增殖的抑制作用无关。虽然浓度高于10 nM的PGE2会导致淋巴细胞增殖受到抑制，但淋巴细胞培养基中测得的PGE2浓度（0.3 - 4 nM）并无抑制作用。PGE3除了在高浓度（大于250 nM）时外，不会抑制淋巴细胞增殖。PGE2或PGE3对增殖的最大抑制作用小于除肉豆蔻酸或棕榈酸外的每种脂肪酸所引起的抑制作用。在培养基中加入磷脂酶A2、环氧化酶或脂氧合酶的抑制剂并不能阻止脂肪酸对淋巴细胞增殖发挥抑制作用。淋巴结细胞培养物中存在的类花生酸源自巨噬细胞而非淋巴细胞。通过贴壁从细胞制剂中去除巨噬细胞并不能阻止脂肪酸抑制增殖。不含巨噬细胞的胸导管淋巴细胞的增殖受到脂肪酸的抑制程度与淋巴结淋巴细胞的增殖相似。这些观察结果提供了令人信服的证据，表明脂肪酸对淋巴细胞增殖的抑制作用与类花生酸的产生无关。因此，如果要在生化水平上理解脂肪酸对淋巴细胞增殖的影响，就必须研究其他机制。
