Malygin A M, Meri S, Timonen T
Department of Pathology, University of Helsinki, Finland.
Scand J Immunol. 1993 Jan;37(1):71-6. doi: 10.1111/j.1365-3083.1993.tb01667.x.
The separate and combined effects of transforming growth factor-beta 1 (TGF-beta 1) and prostaglandin E2 on human natural killer (NK) activity were studied. Peripheral blood lymphocytes (PBL) and large granular lymphocytes (LGL, 70-90% purity) were used as effector cells and K562 as targets. Overnight incubation of the effector cells with TGF-beta 1 resulted in a significant inhibition of NK activity. TGF-beta 1 did not influence the expression of CD3, CD16, CD18 or CD56 antigens on PBL. Combination of TGF-beta 1 with indomethacin gave the same NK-suppressive effect as TGF-beta 1 alone, showing that the inhibition of NK activity by TGF-beta 1 is not due to an increase in PGE2 levels. TGF-beta did not influence cAMP level in PBL whereas PGE2 significantly increased it. On the other hand, TGF-beta 1 and PGE2 showed an additive inhibitory effect on NK activity. TGF-beta 1 did not reduce the binding of PBL and LGL to K562. PGE2 suppressed the binding and TGF-beta 1 did not influence this suppression. TGF-beta 1 also suppressed IL-2-induced activation of NK activity and increase of expression of the granule proteins granzyme A and perforin. PGE2 did not appear to affect granzyme A and perforin contents. The results indicate that TGF-beta 1 and PGE2 suppress NK activity by different mechanisms.
研究了转化生长因子-β1（TGF-β1）和前列腺素E2对人自然杀伤（NK）活性的单独及联合作用。外周血淋巴细胞（PBL）和大颗粒淋巴细胞（LGL，纯度70 - 90%）用作效应细胞，K562用作靶细胞。效应细胞与TGF-β1过夜孵育导致NK活性显著抑制。TGF-β1不影响PBL上CD3、CD16、CD18或CD56抗原的表达。TGF-β1与吲哚美辛联合使用产生的NK抑制作用与单独使用TGF-β1相同，表明TGF-β1对NK活性的抑制不是由于PGE2水平升高所致。TGF-β不影响PBL中的cAMP水平，而PGE2可使其显著升高。另一方面，TGF-β1和PGE2对NK活性表现出相加抑制作用。TGF-β1不降低PBL和LGL与K562的结合。PGE2抑制这种结合，而TGF-β1不影响这种抑制作用。TGF-β1还抑制IL-2诱导的NK活性激活以及颗粒蛋白颗粒酶A和穿孔素表达的增加。PGE2似乎不影响颗粒酶A和穿孔素的含量。结果表明，TGF-β1和PGE2通过不同机制抑制NK活性。
