Comparative analysis of integrin expression on monocyte-derived macrophages and monocyte-derived dendritic cells

Comparative analysis of integrin expression on monocyte-derived macrophages and monocyte-derived dendritic cells
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DOI:
10.1046/j.1365-2567.2000.00056.x
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发表时间:
2000-07-01
期刊:
影响因子:
6.4
通讯作者:
Kreutz, M
Kreutz, M
中科院分区:
医学2区
文献类型:
--
作者:
Ammon, C;Meyer, SP;Kreutz, M

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巨噬细胞(MAC)和树突状细胞(DC)都是单核吞噬细胞系统(MPS)的成员,单核细胞(MO)是共同的前体细胞。 MPS 细胞能够摄取、处理抗原并将其呈递给 T 淋巴细胞,从而诱导初级或次级免疫反应。粘附分子对于抗原呈递细胞与免疫细胞(尤其是 T 淋巴细胞)的相互作用至关重要。通过代表性差异分析,我们将 CD49c (VLA-3)(粘附受体 β(1)-整合素家族的成员)鉴定为 MO 衍生 MAC 中的分化相关抗原。相反,MO衍生的DC不表达CD49c mRNA。这些数据促使我们比较 MAC 和 DC 的整合素表达模式。两种细胞类型均显示 β(1)-整合素 CD49a、CD49b、CD49d 和 CD49e 的 α 链表达较低,而 CD49c 和 CD49f 则观察到显着差异。在 MO 向 MAC 分化期间,两种整合素的表达均增加,但在 DC 上未检测到。与此同时,β(1) 链 (CD29) 在 MO 向 MAC 分化过程中明显上调,但在 DC 上仅微弱表达。另一方面,β(2)-整合素CD11a、CD11b、CD11c和CD18均在MAC和DC上表达。除了在细胞间相互作用和粘附中的作用外,β(2)-整合素还被认为是细菌和脂多糖 (LPS) 的可能结合分子,特别是对于高 LPS 浓度。因此,我们研究了 MAC 与 DC 在肿瘤坏死因子-α (TNF-α) 释放方面的 LPS 反应。 DC 对低剂量 LPS 的反应较差,这可以很容易地用与 MAC 相比 DC 上非常低的 CD14 表达来解释。相反,当用高LPS浓度刺激DC时,TNF-α反应与MAC相当。我们的结果显示了体外生成的 MAC 和 DC 上 β(1) 和 β(2) 整合素表达的特异性、分化依赖性模式。我们认为DC上CD11/CD18的高表达可能参与了DC与LPS的结合。由于LPS不仅是DC的激活剂,而且还是DC的分化刺激物,因此DC上CD11/CD18的表达可能对于DC的成功成熟并从而启动初级免疫反应很重要。
Both macrophages (MAC) and dendritic cells (DC) are members of the mononuclear phagocyte system (MPS) with monocytes (MO) as common precursor cells. Cells of the MPS are able to take up, process and present antigens to T lymphocytes, thereby inducing a primary or secondary immune response. Adhesion molecules are of crucial importance for the interaction of antigen-presenting cells with immune cells, especially T lymphocytes. By representational difference analysis, we identified CD49c (VLA-3), a member of the beta(1)-integrin family of adhesion receptors, as differentiation-associated antigen in MO-derived MAC. In contrast, MO-derived DC did not express CD49c mRNA. These data prompted us to compare the integrin expression pattern of MAC and DC. Both cell types showed a low expression of the alpha-chains of the beta(1)-integrins CD49a, CD49b, CD49d and CD49e, whereas a marked difference was observed for CD49c and CD49f. Expression of both integrins increased during MO to MAC differentiation, but was not detectable on DC. In parallel the beta(1)-chain (CD29) was clearly up-regulated during MO to MAC differentiation but was only weakly expressed on DC. On the other hand, the beta(2)-integrins CD11a, CD11b, CD11c and CD18 were all expressed on MAC and DC. Beside their role in cell-cell interaction and adhesion, beta(2)-integrins are also known as possible binding molecules for bacteria and lipopolysaccharide (LPS), especially for high LPS concentrations. Therefore we investigated the LPS response of MAC versus DC in terms of tumour necrosis factor-alpha (TNF-alpha) release. DC were less responsive to low doses of LPS, which can easily be explained by the very low CD14 expression on DC compared for MAC. In contrast, the TNF-alpha response was comparable to MAC when DC were stimulated with high LPS concentrations. Our results show a specific, differentiation-dependent pattern of beta(1)- and beta(2)-integrin expression on in vitro-generated MAC and DC. We suggest that the high expression of CD11/CD18 on DC could be involved in the LPS binding of DC. As LPS is not only an activation but also a differentiation stimulus for DC, the expression of CD11/CD18 on DC may be important for the successful maturation of DC and thereby the initiation of a primary immune response.