Sozzani S, Luini W, Borsatti A, Polentarutti N, Zhou D, Piemonti L, D'Amico G, Power C A, Wells T N, Gobbi M, Allavena P, Mantovani A
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
J Immunol. 1997 Aug 15;159(4):1993-2000.
Dendritic cells (DC) are migratory cells that exhibit complex trafficking properties in vivo. The present study was designed to characterize receptor expression and responsiveness to chemoattractants of human DC obtained from PBMC by culture with granulocyte/macrophage-CSF and IL-13. DC expressed appreciable levels of the CCR1, CCR2, and CCR5 receptors for the CC chemokines and the chemokine receptors CXCR1, CXCR2, and CXCR4. DC increased intracellular free calcium and migrated in response to the CC chemokines MCP-3, MCP-4, RANTES, MIP-1alpha, MIP-1beta, and MIP-5/HCC2 and the CXC chemokine SDF-1. In contrast, the CC chemokines MCP-1 and eotaxin had little or no activity in the concentration range tested (up to 1 microg/ml). IL-8 and Gro-beta (CXC) and lymphotactin (C chemokines) were also inactive. DC did not respond to 5-HETE, whereas platelet-activating factor was an active agonist. Selected chemokines active on DC in terms of migration and calcium fluxes were examined for their capacity to modulate endocytosis and Ag presentation. Under conditions in which TNF-alpha was active, MCP-1, MCP-3, MIP-1alpha, and RANTES did not affect these two responses. Thus, among hemopoietic elements, DC respond to a unique set of CC and CXC chemokines, and their responsiveness is restricted to migration with no effect on Ag capture and presentation. Chemokines may play a role in the trafficking of DC under resting or stimulated conditions. Chemokine receptors expressed in DC are likely to underlie HIV infection of this cell type.
树突状细胞（DC）是在体内具有复杂迁移特性的游走细胞。本研究旨在通过用粒细胞/巨噬细胞集落刺激因子和白细胞介素-13培养从外周血单核细胞获得的人DC，来表征其受体表达及对趋化因子的反应性。DC表达了可观水平的CC趋化因子的CCR1、CCR2和CCR5受体以及趋化因子受体CXCR1、CXCR2和CXCR4。DC细胞内游离钙增加，并对CC趋化因子MCP-3、MCP-4、RANTES、MIP-1α、MIP-1β和MIP-5/HCC2以及CXC趋化因子SDF-1产生迁移反应。相比之下，CC趋化因子MCP-1和嗜酸性粒细胞趋化因子在测试浓度范围（高达1微克/毫升）内几乎没有活性或无活性。IL-8和Gro-β（CXC）以及淋巴细胞趋化因子（C趋化因子）也无活性。DC对5-羟二十碳四烯酸无反应，而血小板活化因子是一种活性激动剂。就迁移和钙通量而言，对作用于DC的选定趋化因子调节内吞作用和抗原呈递的能力进行了检测。在肿瘤坏死因子-α有活性的条件下，MCP-1、MCP-3、MIP-1α和RANTES不影响这两种反应。因此，在造血细胞成分中，DC对一组独特的CC和CXC趋化因子有反应，并且它们的反应性仅限于迁移，对抗原捕获和呈递无影响。趋化因子可能在静息或刺激条件下DC的迁移中起作用。DC中表达的趋化因子受体可能是该细胞类型感染HIV的基础。
