Delgado E, Finkel V, Baggiolini M, Mackay C R, Steinman R M, Granelli-Piperno A
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY, USA.
Immunobiology. 1998 Mar;198(5):490-500. doi: 10.1016/s0171-2985(98)80073-9.
Immature dendritic cells (DCs) are highly motile, but after differentiation they stop migration. Chemokines are chemotactic cytokines that direct leukocyte trafficking, therefore we looked for the expression and function of chemokine receptors in immature and mature DCs. As a model, we used the human DCs that develop from CD14+ peripheral blood monocytes cultured with GM-CSF and IL-4. After 6-7 days in culture, these cells have the characteristics of immature DCs, but can be induced to mature further by inflammatory stimuli or by monocyte conditioned medium (MCM). Immature DCs express mRNA for CXCR4, CCR3 and CCR5. The receptors are expressed on the cell surface, as assessed with monoclonal antibodies, and are functional (with the exception of CCR3) as assessed by CA++ mobilization in response to specific chemokines. Further differentiation and maturation of DC in MCM causes a downregulation of expression and function of the beta-chemokine receptors, while CXCR4 still remains, and signals a calcium flux on mature DCs. We argue that the downregulation of beta-chemokine receptors during maturation helps to stop DC movement after T cells have been identified in lymphoid organs or at sites of delayed-type hypersensitivity.
未成熟树突状细胞（DCs）具有高度的迁移能力，但分化后它们就停止迁移。趋化因子是指导白细胞迁移的趋化性细胞因子，因此我们研究了趋化因子受体在未成熟和成熟DCs中的表达及功能。作为模型，我们使用了由用GM-CSF和IL-4培养的CD14+外周血单核细胞发育而来的人DCs。培养6-7天后，这些细胞具有未成熟DCs的特征，但可通过炎性刺激或单核细胞条件培养基（MCM）进一步诱导成熟。未成熟DCs表达CXCR4、CCR3和CCR5的mRNA。用单克隆抗体评估，这些受体在细胞表面表达，并且通过响应特定趋化因子的Ca++动员评估，它们是有功能的（CCR3除外）。DCs在MCM中进一步分化和成熟导致β-趋化因子受体的表达和功能下调，而CXCR4仍然存在，并在成熟DCs上发出钙流信号。我们认为，成熟过程中β-趋化因子受体的下调有助于在淋巴器官或迟发型超敏反应部位识别T细胞后停止DC的移动。
