Bostan Marinela, Constantin Mariana Claudia, Nicolau Adriana, Hirt Mirela, Galatiuc Ceciclia, Matei I, Braşoveanu Lorelei Irina, Iordăchescu Dana
St. S. Nitcolau Institute of Virology Center of Immunology, Bucharest, Romania.
Roum Arch Microbiol Immunol. 2002 Oct-Dec;61(4):243-58.
Neutrophils are the predominant cells accumulated in the synovial fluid (SF) of rheumatoid arthritis (RA) patients. Accumulation of neutrophils may be regarded as a possible way by which neutrophils exert cytotoxic functions. The aim of the present study was to analyze the chemotactic response of neutrophils (PMNs) isolated from the peripheral blood or SF of patients with RA by performing the chemotaxis assay, in which N-formyl-methionyl-leucyl-phenylalanine (FMLP) was used as chemotactic agent. Our results showed that FMLP induced response of peripheral blood neutrophils from 12 patients with RA was similar with the response of 15 healthy controls. A decreased chemotactic response to FMLP was, however, observed in PMNs isolated from the SF of RA patients as comlipared with peripheral blood cells. Therefore, this defective chemotactic ability of neutrophil, was inversely correlated with the number of infiltrating cells in SF. These results indicate that chemotactic ability of neutrophils may be reduced after migration to the SF. Because PMNs chemotaxis in vivo has likely occurred in the presence of serum or SF, we tried to simulate the same conditions in vitro. Therefore, we analyzed the effect of serum or SF on the RA-PMNs chemotaxis. Heat-inactivated serum produced a marked reduction of chemotactic activity developed by PMNs isolated from patients with RA. Notably, a significant increase of chemotactic activity was observed when FMLP and serum stimuli were used together, as compared with the same stimuli used alone. The results suggested that complement activation might interfere with neutrophils chemotaxis. SF amplifies the chemotactic activity of PMNs isolated from peripheral blood of RA patients, but does not affect the chemotaxis developed by PMNs isolated from SF. The data might suggest that several components of SF (IL-8, leukotrien B4, thrombin, platelet-activating factor, etc.) could serve as a potent stimulus for recruitment of neutrophils from periphery into the RA joint. In conclusion, serum or SF components seem to contribute to chemotaxis of neutrophils and play a role in differential killing of PMNs and incidence of infection.
中性粒细胞是类风湿关节炎（RA）患者滑液（SF）中积聚的主要细胞。中性粒细胞的积聚可能被视为中性粒细胞发挥细胞毒性功能的一种可能方式。本研究的目的是通过进行趋化性分析来分析从RA患者外周血或SF中分离出的中性粒细胞（PMN）的趋化反应，其中使用N-甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）作为趋化剂。我们的结果表明，FMLP诱导的12例RA患者外周血中性粒细胞的反应与15例健康对照者的反应相似。然而，与外周血细胞相比，在从RA患者SF中分离出的PMN中观察到对FMLP的趋化反应降低。因此，中性粒细胞这种有缺陷的趋化能力与SF中浸润细胞的数量呈负相关。这些结果表明，中性粒细胞迁移到SF后其趋化能力可能会降低。由于PMN在体内的趋化作用可能是在血清或SF存在的情况下发生的，我们试图在体外模拟相同的条件。因此，我们分析了血清或SF对RA-PMN趋化作用的影响。热灭活血清使从RA患者分离出的PMN产生的趋化活性显著降低。值得注意的是，与单独使用相同刺激物相比，当同时使用FMLP和血清刺激时，观察到趋化活性显著增加。结果表明补体激活可能会干扰中性粒细胞的趋化作用。SF增强了从RA患者外周血分离出的PMN的趋化活性，但不影响从SF中分离出的PMN产生的趋化作用。数据可能表明SF的几种成分（白细胞介素-8、白三烯B4、凝血酶、血小板活化因子等）可作为将中性粒细胞从外周募集到RA关节的有效刺激物。总之，血清或SF成分似乎有助于中性粒细胞的趋化作用，并在PMN的差异杀伤和感染发生率中发挥作用。
