Interferon-inducible protein-10 and lymphotactin induce the chemotaxis and mobilization of intracellular calcium in natural killer cells through pertussis toxin-sensitive and -insensitive heterotrimeric G-proteins
Interferon-inducible protein-10 and lymphotactin induce the chemotaxis and mobilization of intracellular calcium in natural killer cells through pertussis toxin-sensitive and -insensitive heterotrimeric G-proteins
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DOI：
10.1096/fasebj.11.10.9271361
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发表时间：
1997-08-01
期刊：
影响因子：
4.8
通讯作者：
AlAoukaty, A
中科院分区：
文献类型：
--
作者：
Maghazachi, AA;Skalhegg, BS;AlAoukaty, A
我们在这里发现干扰素诱导蛋白-10 (IP-10)，一种缺乏CXC趋化因子的ELR和C趋化因子淋巴趋化素（Ltn）在il -2激活的NK细胞（IANK）和CC趋化因子激活的NK细胞（CHAK）中诱导趋化和钙动员。交叉脱敏实验表明，IP-10或Ltn使用的受体与其他C、CC或CXC趋化因子不同。在百日咳毒素（PT）预处理这些细胞后，IP-10或Ltn诱导的两种细胞类型的趋化性均被抑制。此外，Ltn诱导的IANK而非CHAK细胞中的[Ca2+](i)在PT预处理后被抑制，而IP-10诱导的IANK和CHAK细胞中的[Ca2+](i)在该毒素预处理后被抑制。这些结果表明，pt敏感和pt不敏感的G蛋白在ip -10诱导和ltn诱导的活化NK细胞的趋化性和钙流中发挥重要作用，这在CHAK和IANK细胞的溶血素O渗透以及引入pt敏感G(i)和G(O)或pt不敏感G(q)的抑制抗体后进一步得到证实。我们的研究结果表明，IP-10和Ltn受体在IANK细胞中与G(i)、G(o)和G(q)偶联，在CHAX细胞中与G(o)和G(q)偶联，在这些细胞中IP-10受体与G(o)的偶联可能很低，而Ltn受体与G(o)的偶联可能不高。总之，这些结果表明IP-10和Ltn依赖性趋化和钙动员可能在受体偶联到异三聚体G蛋白的水平上发生分化。
We show here that interferon-inducible protein-10 (IP-10), an ELR lacking CXC chemokine, and the C chemokine lymphotactin (Ltn) induce the chemotaxis and calcium mobilization in IL-2-activated NK (IANK) and CC chemokine-activated NK (CHAK) cells. Cross-desensitization experiments show that IP-10 or Ltn use receptors not shared by other C, CC, or CXC chemokines. The chemotaxis induced by either IP-10 or Ltn for both cell types is inhibited upon pretreatment of these cells with pertussis toxin (PT), Also, Ltn-induced [Ca2+](i) in IANK but not in CHAK cells is inhibited upon pretreatment with PT, whereas IP-10-induced [Ca2+](i) in IANK and CHAK cells is inhibited upon pretreatment with this toxin, These results suggest important roles for PT-sensitive and -insensitive G-proteins in IP-10-induced and Ltn-induced chemotaxis and calcium fluxes in activated NK cells, This was further implicated after streptolysin O permeabilization of CHAK and IANK cells and after introduction of inhibitory antibodies to the PT-sensitive G(i) and G(o) or the PT-insensitive G(q). Our results suggest that IP-10 and Ltn receptors are coupled to G(i), G(o), and G(q) in IANK cells and to G(i) and G(q) in CHAX cells, with a possible low coupling of IP-10, but not of Ltn, receptors to G(o) in these cells, Together, these results show that IP-10 and Ltn-dependent chemotaxis and calcium mobilization may differentiate at the level of receptor coupling to the heterotrimeric G-proteins.