Cytokine induction of the ability of human monocyte CD44 to bind hyaluronan is mediated primarily by TNF-alpha and is inhibited by IL-4 and IL-13.
Cytokine induction of the ability of human monocyte CD44 to bind hyaluronan is mediated primarily by TNF-alpha and is inhibited by IL-4 and IL-13.
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DOI：
10.4049/jimmunol.159.12.6184
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发表时间：
1997-12
影响因子：
4.4
通讯作者：
M. Levesque;B. Haynes
中科院分区：
文献类型：
--
作者：
M. Levesque;B. Haynes
透明质酸（HA）连接CD 44是调节淋巴细胞和单核细胞粘附和细胞因子产生的关键促炎事件。虽然大多数免疫细胞表达CD 44，但很少有免疫细胞组成型结合HA。我们以前已经表明，单核细胞CD 44获得的能力，结合HA后，在人血清中的PBMC体外培养，因此，我们已经研究了一系列的人细胞因子和细菌LPS诱导和/或抑制单核细胞CD 44结合HA的能力。我们发现IL-1 α、IL-1 β、IL-3、粒细胞巨噬细胞（GM）-CSF和TNF-α以及细菌LPS都直接诱导外周血单核细胞与HA结合。相反，IL-2和IL-15上调PBMC悬浮液中单核细胞CD 44 HA结合，但在纯化的单核细胞悬浮液中不上调。抗TNF-α中和抗体抑制IL-1 α、IL-1 β、IL-3和GM-CSF介导的单核细胞HA结合。此外，用抗TNF-α Ab处理IL-2和IL-15刺激的PBMC培养物可阻止IL-2和IL-15诱导的单核细胞HA结合，从而鉴定TNF-α为作用于单核细胞以诱导HA结合的淋巴细胞衍生因子。相反，IL-4和IL-13是人血清或IL-1 α、IL-1 β、IL-3、GM-CSF或TNF-α诱导的单核细胞CD 44-HA结合的有效抑制剂。IL-10对单核细胞CD 44-HA结合具有双重作用。IL-10单独诱导HA与PBMC单核细胞CD 44结合，而相反，IL-10抑制IL-1诱导的单核细胞CD 44与HA结合。总之，这些研究鉴定了T细胞和单核细胞衍生的细胞因子的网络，其主要通过TNF-α调节HA与外周血单核细胞CD 44的结合。
Ligation of CD44 by hyaluronan (HA) is a key proinflammatory event that regulates lymphocyte and monocyte adhesion and cytokine production. While most immune cells express CD44, few immune cells constitutively bind HA. We have previously shown that monocyte CD44 acquires the ability to bind HA after in vitro culture of PBMC in human serum and, therefore, we have investigated a series of human cytokines and bacterial LPS for their ability to induce and/or inhibit monocyte CD44 to bind HA. We found that IL-1alpha, IL-1beta, IL-3, granulocyte macrophage (GM)-CSF, and TNF-alpha, as well as bacterial LPS, all directly induced peripheral blood monocytes to bind HA. In contrast, IL-2 and IL-15 up-regulated monocyte CD44 HA-binding in PBMC suspensions, but not in purified monocyte suspensions. An anti-TNF-alpha-neutralizing Ab inhibited IL-1alpha-, IL-1beta-, IL-3-, and GM-CSF-mediated monocyte HA binding. In addition, treatment of IL-2- and IL-15-stimulated PBMC cultures with an anti-TNF-alpha Ab prevented IL-2- and IL-15-induced monocyte HA binding, thus identifying TNF-alpha as a lymphocyte-derived factor that acted on monocytes to induce HA binding. In contrast, IL-4 and IL-13 were potent inhibitors of monocyte CD44-HA binding induced by either human serum or by IL-1alpha, IL-1beta, IL-3, GM-CSF, or TNF-alpha. IL-10 had dual effects on monocyte CD44-HA binding. Alone, IL-10 induced HA binding to PBMC monocyte CD44, while in contrast, IL-10 inhibited IL-1-induced monocyte CD44 binding to HA. Taken together, these studies identify a network of T cell and monocyte-derived cytokines that regulate HA binding to peripheral blood monocyte CD44, primarily through TNF-alpha.