Vaillier D, Daculsi R, Gualde N, Bezian J H
Laboratoire d'Immunologie, Université de Bordeaux II, France.
Cell Immunol. 1992 Jan;139(1):248-58. doi: 10.1016/0008-8749(92)90117-8.
NK activity is regulated by arachidonic acid metabolites. More precisely PGE2 and LTB4 decreases and increases respectively non-MHC-restricted cytotoxicity in humans. We have observed similar data in mice since NK activity was inhibited by PGE2 (10(-6) to 10(-8) M) and enhanced by LTB4 (10(-8) to 10(-12) M). On the other hand when PGE2 and LTB4 were combined during the same assay the lysis percentage was smaller than the one which was induced by PGE2 alone. Because PGE2 increases intracellular cyclic AMP and that LTB4 augments cyclic GMP we used a cAMP inducer (forskolin) and a cGMP analogue (8 Br-cGMP) instead of eicosanoids and we observed similar data (i.e., a decrease of natural killing) as when PGE2 was combined with LTB4. When splenocytes are cultured for 1-4 days alone, cytotoxic activity decreases unless they are cultured in the presence of indomethacin. Cytotoxic activity of spleen cells cultured in the presence of PGE2 or LTB4 is respectively decreased or increased. However, splenocytes that were cultured alone for at least 24 hr were no longer sensitive to inhibition by PGE2 but were still PGE2-sensitive when cultured in the presence of LTB4.
自然杀伤(NK)活性受花生四烯酸代谢产物调节。更确切地说,前列腺素E2(PGE2)和白三烯B4(LTB4)分别降低和增强人类非主要组织相容性复合体(MHC)限制的细胞毒性。我们在小鼠中也观察到了类似的数据,因为PGE2(10^(-6)至10^(-8)M)抑制NK活性,而LTB4(10^(-8)至10^(-12)M)增强NK活性。另一方面,当在同一实验中同时使用PGE2和LTB4时,裂解百分比低于单独使用PGE2时诱导的裂解百分比。由于PGE2增加细胞内环磷酸腺苷(cAMP),而LTB4增加环磷酸鸟苷(cGMP),我们使用一种cAMP诱导剂(福斯高林)和一种cGMP类似物(8-溴-cGMP)代替类二十烷酸,并且我们观察到了与PGE2和LTB4联合使用时类似的数据(即自然杀伤作用降低)。当脾细胞单独培养1 - 4天时,细胞毒性活性降低,除非在吲哚美辛存在的情况下培养。在PGE2或LTB4存在下培养的脾细胞的细胞毒性活性分别降低或增加。然而,单独培养至少24小时的脾细胞对PGE2的抑制不再敏感,但在LTB4存在下培养时仍对PGE2敏感。