Menten P, Proost P, Struyf S, Van Coillie E, Put W, Lenaerts J P, Conings R, Jaspar J M, De Groote D, Billiau A, Opdenakker G, Van Damme J
Rega Institute, Laboratory of Molecular Immunology, University of Leuven, Belgium.
Eur J Immunol. 1999 Feb;29(2):678-85. doi: 10.1002/(SICI)1521-4141(199902)29:02<678::AID-IMMU678>3.0.CO;2-J.
Monocyte chemotactic protein-3 (MCP-3) is a pluripotent CC chemokine, attracting most leukocytic cell types. With the use of a sensitive and specific ELISA, MCP-3 was found to be inducible in fibroblasts and peripheral blood mononuclear cells (PBMC) by cytokines and cytokine inducers. MCP-3 production levels (1-10 ng/ml) were tenfold lower compared to those of MCP-1. In diploid fibroblasts, synergistic induction of MCP-3, but not of MCP-1, mRNA and protein was observed by combined treatment with IL-1beta and IFN-gamma. In PBMC, IFN-alpha and IFN-beta (but not IFN-gamma), as well as measles virus and double-stranded RNA, were potent inducers of MCP-3, which suggests a role for this chemokine in an early stage of viral infections. In contrast, endotoxin failed to induce MCP-3 production in fibroblasts and PBMC. Purification of MCP-3 from PBMC revealed biochemical heterogeneity. In monocyte chemotaxis and calcium mobilization assays, pure 11-kDa MCP-3 from PBMC showed similar potencies as MCP-3 from tumor cells. It was concluded that the induction of MCP-3 by IFN is regulated differently in fibroblasts and PBMC. In view of the multiple target cells for MCP-3, local and strictly regulated chemokine production might be important to conduct selectively the immune response in infection or inflammation.
单核细胞趋化蛋白-3（MCP-3）是一种多能CC趋化因子，可吸引大多数白细胞类型。通过使用灵敏且特异的酶联免疫吸附测定（ELISA），发现细胞因子和细胞因子诱导剂可在成纤维细胞和外周血单核细胞（PBMC）中诱导产生MCP-3。与MCP-1相比，MCP-3的产生水平（1 - 10 ng/ml）低了10倍。在二倍体成纤维细胞中，通过白细胞介素-1β（IL-1β）和γ干扰素（IFN-γ）联合处理，可观察到MCP-3而非MCP-1的mRNA和蛋白质的协同诱导。在PBMC中，α干扰素（IFN-α）和β干扰素（IFN-β）（而非IFN-γ），以及麻疹病毒和双链RNA，是MCP-3的有效诱导剂，这表明该趋化因子在病毒感染早期发挥作用。相比之下，内毒素未能在成纤维细胞和PBMC中诱导MCP-3的产生。从PBMC中纯化的MCP-3显示出生化异质性。在单核细胞趋化和钙动员试验中，来自PBMC的纯11 kDa MCP-3与来自肿瘤细胞的MCP-3表现出相似的效力。得出的结论是，IFN对MCP-3的诱导在成纤维细胞和PBMC中的调控方式不同。鉴于MCP-3有多种靶细胞，局部且严格调控的趋化因子产生对于在感染或炎症中选择性地引导免疫反应可能很重要。
