Ammon C, Meyer S P, Schwarzfischer L, Krause S W, Andreesen R, Kreutz M
Department of Haematology and Oncology, University of Regensburg, Regensburg, Germany.
Immunology. 2000 Jul;100(3):364-9. doi: 10.1046/j.1365-2567.2000.00056.x.
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 beta1-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 beta1-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 beta1-chain (CD29) was clearly up-regulated during MO to MAC differentiation but was only weakly expressed on DC. On the other hand, the beta2-integrins CD11a, CD11b, CD11c and CD18 were all expressed on MAC and DC. Beside their role in cell-cell interaction and adhesion, beta2-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 beta1- and beta2-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.
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）是它们的共同前体细胞。MPS的细胞能够摄取、处理抗原并将其呈递给T淋巴细胞，从而诱导初次或二次免疫反应。黏附分子对于抗原呈递细胞与免疫细胞（尤其是T淋巴细胞）之间的相互作用至关重要。通过代表性差异分析，我们确定CD49c（VLA-3），一种黏附受体β1整合素家族的成员，为MO来源的MAC中的分化相关抗原。相比之下，MO来源的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β1整合素CD49a、CD49b、CD49d和CD49e的α链表达较低，而CD49c和CD49f则存在明显差异。在MO向MAC分化过程中，这两种整合素的表达均增加，但在DC上未检测到。同时，β1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，β2整合素CD11a、CD11b、CD11c和CD18在MAC和DC上均有表达。除了在细胞间相互作用和黏附中的作用外，β2整合素还被认为是细菌和脂多糖（LPS）的可能结合分子，尤其是对于高浓度的LPS。因此，我们从肿瘤坏死因子-α（TNF-α）释放的角度研究了MAC与DC对LPS的反应。DC对低剂量LPS的反应较弱，这很容易通过与MAC相比DC上极低的CD14表达来解释。相反，当用高浓度LPS刺激DC时，其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β1和β2整合素表达的特定、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，也是其分化刺激剂，DC上CD11/CD18的表达可能对DC的成功成熟以及从而引发初次免疫反应很重要。
