Fricke Ingo, Mitchell Daniell, Petersen Frank, Böhle Andreas, Bulfone-Paus Silvia, Brandau Sven
Division of Immunotherapy, Research Center Borstel, Borstel, Germany.
FASEB J. 2004 Oct;18(13):1588-90. doi: 10.1096/fj.03-1435fje. Epub 2004 Aug 19.
Recent evidence suggests that platelets are not only involved in haemostatic processes but also modulate immune responses. As antigen-presenting cells (APC) are of crucial importance for the regulation of immunity, in this study we wanted to define the role of platelet factor 4 (PF-4) as one of the major platelet-derived chemokines on the transition of monocytes into APCs. Our experiments show that within 3 days PF-4 in conjunction with IL-4 induces a rapid differentiation of monocytes into APC. These PFAPC (PF-4/IL-4 differentiated APC) display unique phenotypical and functional characteristics setting them apart from macrophages and conventional dendritic cells. Functional studies revealed that PFAPC preferentially stimulated proliferation of lymphocytes and lytic NK activity while they induced only moderate cytokine responses. Beyond day 3 of differentiation, PFAPC became less immunostimulatory and maintained their capacity to phagocytose particulate material even after LPS-induced maturation. These experiments uncover a previously unknown role for the platelet-derived CXC-chemokine PF-4 in differentiation of human APC. Our data further support the newly discovered function of platelets in immunomodulation and provide new evidence for a rapid transition of monocytes into APC under the influence of inflammatory stimuli.
最近的证据表明，血小板不仅参与止血过程，还能调节免疫反应。由于抗原呈递细胞（APC）对免疫调节至关重要，在本研究中，我们希望确定血小板因子4（PF-4）作为主要的血小板衍生趋化因子之一在单核细胞向APC转变过程中的作用。我们的实验表明，在3天内，PF-4与IL-4共同作用可诱导单核细胞迅速分化为APC。这些PFAPC（PF-4/IL-4分化的APC）表现出独特的表型和功能特征，使其有别于巨噬细胞和传统树突状细胞。功能研究表明，PFAPC优先刺激淋巴细胞增殖和NK细胞的裂解活性，而它们仅诱导适度的细胞因子反应。在分化3天后，PFAPC的免疫刺激作用减弱，即使在LPS诱导成熟后仍保持吞噬颗粒物质的能力。这些实验揭示了血小板衍生的CXC趋化因子PF-4在人类APC分化中以前未知的作用。我们的数据进一步支持了血小板在免疫调节中的新发现功能，并为炎症刺激影响下单核细胞向APC的快速转变提供了新证据。
