Regulation of human natural killer (NK) cell function: induction of killing of an NK-resistant renal carcinoma cell line.

Regulation of human natural killer (NK) cell function: induction of killing of an NK-resistant renal carcinoma cell line.
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人类自然杀伤 (NK) 细胞功能的调节:诱导杀伤 NK 耐药性肾癌细胞系。

DOI:
10.1007/bf00915159
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发表时间:
1988
影响因子:
9.1
通讯作者:
Lipsky,PE
Lipsky,PE
中科院分区:
医学2区
文献类型:
--
作者:
Kanar,MC;Thiele,DL;Ostensen,M;Lipsky,PE

文献摘要

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评估了针对肾癌细胞系Cur的自然杀伤(NK)样活性。在4小时试验中,人外周血单核细胞未自发杀伤Cur细胞。在18小时试验中观察到Cur杀伤,但杀伤幅度可变,且始终明显低于对K562的杀伤。Cur杀伤介导的非粘附,非吞噬细胞的淋巴细胞,其活性可以调制积极和消极的单核细胞或其产品。将效应子与单核细胞上清液、白细胞介素1(IL-1)、α-干扰素(αIFN)或白细胞介素2(IL-2)预孵育,可大大增加Cur杀伤的幅度,并加速溶解动力学。在IL-2体外激活NK细胞的过程中,加入前列腺素E_2(PGE_2)可显著抑制随后的Cur裂解,而对K562裂解的抑制作用很小。然而,在用IL-2活化后,Cur靶的裂解对PGE 2的抑制作用不太敏感。去除Leu 11b(+)、OKM 1(+)或l-亮氨酰亮氨酸甲酯敏感细胞显著降低Cur和K562溶解。此外,发现用荧光激活细胞分选仪纯化的CD 16(+)细胞介导Cur杀伤。尽管Cur和K562裂解是由表型相似的效应细胞介导的,但本研究表明,由裂解这两种靶点的能力定义的细胞毒性功能在响应各种免疫调节刺激时不同。
Natural killer (NK)-like activity against a renal carcinoma cell line, Cur, was assessed. There was no spontaneous killing of Cur cells by human peripheral blood mononuclear cells in 4-hr assays. Cur killing was observed in 18-hr assays, but the magnitude of killing was variable and always markedly less than that against K562. Cur killing was mediated by a nonadherent, nonphagocytic lymphocyte, the activity of which could be modulated both positively and negatively by monocytes or their products. Preincubation of effectors with monocyte supernatant, interleukin 1 (IL-1), α-interferon (αIFN), or interleukin 2 (IL-2) greatly increased the magnitude of Cur killing and accelerated the kinetics of lysis. The addition of prostaglandin E2(PGE2) duringin vitroactivation of NK by IL-2 profoundly inhibited subsequent Cur lysis, whereas only minimal inhibition of K562 lysis was noted. However, following activation with IL-2, lysis of Cur targets was less sensitive to the inhibitory effects of PGE2. Removal of Leu 11b(+), OKM1(+), orl-leucylleucine methyl ester-sensitive cells markedly decreased both Cur and K562 lysis. Moreover, CD16(+) cells purified with the fluorescence-activated cell sorter were found to mediate Cur killing. Whereas Cur and K562 lysis is mediated by phenotypically similar effector cells, the present studies demonstrate that the cytotoxic functions defined by the ability to lyse these two targets differ in response to a variety of immunoregulatory stimuli.