Interleukin-15 and interferon-gamma participate in the cross-talk between natural killer and monocytic cells required for tumour necrosis factor production.
Interleukin-15 and interferon-gamma participate in the cross-talk between natural killer and monocytic cells required for tumour necrosis factor production.
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DOI：
10.1186/ar1955
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发表时间：
2006
影响因子：
4.9
通讯作者：
Sanchez-Madrid, Francisco
中科院分区：
文献类型：
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作者：
Gonzalez-Alvaro, Isidoro;Dominguez-Jimenez, Carmen;Ortiz, Ana M;Nunez-Gonzalez, Vanessa;Roda-Navarro, Pedro;Fernandez-Ruiz, Elena;Sancho, David;Sanchez-Madrid, Francisco
我们在体外鉴定了单核细胞诱导TNF分泌的淋巴细胞亚群和受体分子。当单核细胞与静息或il -15刺激的淋巴细胞、T细胞、B细胞或自然杀伤（NK）细胞共培养时，从健康人的外周血和炎症性关节病患者的滑液中分离出来，测量单核细胞分泌的TNF。与il -15激活的外周血或滑膜液淋巴细胞共培养可诱导单核细胞在24小时内产生TNF，这一作用主要由NK细胞介导。反过来，单核细胞诱导NK细胞中CD69的表达和IFN-γ的产生，这一作用主要是由β2整合素和膜结合IL-15介导的。此外，IFN-γ增加了单核细胞中膜结合IL-15的产生。阻断β2整合素和膜结合IL-15抑制TNF的产生，而在抗cd48和抗cd244 （2B4）单克隆抗体存在下TNF的合成增加。所有这些发现表明NK细胞和单核细胞之间的串扰导致持续刺激TNF的产生。这种现象可能在类风湿关节炎等疾病的发病机制中很重要，在类风湿关节炎中TNF的合成增强。
We have characterized the lymphocyte subset and the receptor molecules involved in inducing the secretion of TNF by monocytic cells in vitro. The TNF secreted by monocytic cells was measured when they were co-cultured with either resting or IL-15-stimulated lymphocytes, T cells, B cells or natural killer (NK) cells isolated from the peripheral blood of healthy subjects and from the synovial fluid from patients with inflammatory arthropathies. Co-culture with IL-15-activated peripheral blood or synovial fluid lymphocytes induced TNF production by monocytic cells within 24 hours, an effect that was mainly mediated by NK cells. In turn, monocytic cells induced CD69 expression and IFN-γ production in NK cells, an effect that was mediated mainly by β2 integrins and membrane-bound IL-15. Furthermore, IFN-γ increased the production of membrane-bound IL-15 in monocytic cells. Blockade of β2 integrins and membrane-bound IL-15 inhibited TNF production, whereas TNF synthesis increased in the presence of anti-CD48 and anti-CD244 (2B4) monoclonal antibodies. All these findings suggest that the cross-talk between NK cells and monocytes results in the sustained stimulation of TNF production. This phenomenon might be important in the pathogenesis of conditions such as rheumatoid arthritis in which the synthesis of TNF is enhanced.