Jalonen Tuula O, Pulkkinen Kati, Ukkonen Maritta, Saarela Marika, Elovaara Irina
Medical School, University of Tampere.
J Neurol. 2002 May;249(5):576-83. doi: 10.1007/s004150200067.
Chemokines are small chemoattractant cytokines which participate in the migration of immune cells into the CNS and contribute to the T cell-mediated pathogenesis of multiple sclerosis (MS). The expression of chemokines and their receptors in freshly isolated mononuclear cells from peripheral blood (PBMC) was studied in relation to MS subtype, disease duration and progression in a total of 57 patients with MS (22 relapsing remitting, RRMS; 21 secondary progressive, SPMS; 14 primary progressive, PPMS) and 17 healthy controls. The RNA expression of CCR5 in PBMC was analysed by reverse transcription polymerase chain reaction (RT-PCR) using specific oligonucleotide primers. The PBMC levels of CCR5-ligands MIP-1 alpha/beta and RANTES, and chemokines MCP-1, IL-8, lymphotactin, IP-10 and I-309 were analysed by ribonuclease protection assay (RPA). Significantly increased intracellular CCR5 RNA expression intensity was detected in PPMS when compared with SPMS ( p=0.009), RRMS ( p=0.013), and controls ( p=0.023). However, the surface expression of CCR5 on CD4(+) cells from PBMC, analysed by flow cytometry, appeared to be similar in all MS subtypes and controls. The CCR5-ligands RANTES and MIP-1b were expressed constitutively in all patients and controls. Interleukin-8 was found in all MS subtypes and controls, but IP-10 was detected only in RRMS and SPMS, and lymphotactin occasionally in other subtypes but PPMS. MCP-1, MIP-1a or I-309 were not expressed in any of the groups studied. A correlation was found between the RNA levels of RANTES and CCR5 in PPMS ( r=0.735). Differential profile in the expression of CCR5 and chemokines between PPMS and other MS subtypes may contribute to differences in the pathogenesis of MS and thus can be of importance in the development of new treatments for MS.
趋化因子是一类小的化学趋化细胞因子，参与免疫细胞向中枢神经系统的迁移，并在多发性硬化症（MS）的T细胞介导的发病机制中起作用。我们研究了57例MS患者（22例复发缓解型，RRMS；21例继发进展型，SPMS；14例原发进展型，PPMS）和17名健康对照者外周血新鲜分离的单核细胞（PBMC）中趋化因子及其受体的表达与MS亚型、疾病持续时间和进展的关系。使用特异性寡核苷酸引物，通过逆转录聚合酶链反应（RT-PCR）分析PBMC中CCR5的RNA表达。通过核糖核酸酶保护试验（RPA）分析PBMC中CCR5配体MIP-1α/β和RANTES以及趋化因子MCP-1、IL-8、淋巴细胞趋化因子、IP-10和I-309的水平。与SPMS（p = 0.009）、RRMS（p = 0.013）和对照（p = 0.023）相比，PPMS中检测到细胞内CCR5 RNA表达强度显著增加。然而，通过流式细胞术分析，PBMC中CD4(+)细胞上CCR5的表面表达在所有MS亚型和对照中似乎相似。CCR5配体RANTES和MIP-1b在所有患者和对照中均组成性表达。所有MS亚型和对照中均发现白细胞介素-8，但IP-10仅在RRMS和SPMS中检测到，淋巴细胞趋化因子偶尔在其他亚型中检测到，但PPMS中未检测到。MCP-1、MIP-1a或I-309在任何研究组中均未表达。在PPMS中发现RANTES和CCR5的RNA水平之间存在相关性（r = 0.735）。PPMS与其他MS亚型之间CCR5和趋化因子表达的差异可能导致MS发病机制的差异，因此在MS新治疗方法的开发中可能具有重要意义。
