Neidhart M, Pataki F, Fehr K
Department of Rheumatology, University Hospital, Zurich.
Schweiz Med Wochenschr. 1995 Mar 4;125(9):424-8.
Endothelial cells express adhesion molecules and release free forms (e.g., sELAM-1, sGMP-140, sICAM-1 and sVCAM-1). Compared with controls, the serum levels of these soluble adhesion molecules (SAM) were significantly increased in patients with rheumatoid arthritis. We investigated whether this was associated with the circulating cytokines and changes in peripheral blood T-lymphocyte (T-PBL) subsets. In healthy subjects, sELAM-1 correlated with the serum levels of Il-1 beta, Il-1 receptor antagonist (Il-1RA) and Il-6, while sGMP-140 was associated with Il-8, and sVCAM-1 was related to Il-7 and Il-8. Thus, already in controls, relations exist between the levels of SAM and circulating cytokines. The rheumatoid arthritis patients with low and high serum levels of IgA- and/or IgM-rheumatoid factors (RF) were separately analyzed. They have different cytokine profiles and showed distinct correlations. In patients with low RF, sGMP-140 and sVCAM-1 correlated with Il-1 beta, while sICAM-1 was associated with Il-7 and TNF-alpha. In patients with high RF, sELAM-1 correlated with Il-1RA, and sGMP-140 was associated with many cytokines (e.g., GM-CSF, MIP-1 alpha and TNF-alpha). In addition, lymphopenia (less than 1000 lymphocytes/microliters) was shown in 30% of the patients, and 20% (mostly with low RF levels) had reduced levels of "primed" CD45RO+ cells among T-PBL. In controls, cytokines (Il-7, Il-8 and GM-CSF), but not SAM, were associated with less CD45RO+ T-PBL. In patients with low RF only, sGMP-140 and sELAM-1 correlated with the depletion of "primed" CD4+ and CD8+ T-PBL respectively. In such patients, Il-1 beta and GM-CSF also correlated with less CD8+, CD45RO+ T-PBL. Thus, particularly in patients with low RF, increased SAM, possibly released by the endothelial cells, might reflect the cytokine-induced activation of the vascular endothelium and the extravasation of some CD45RO+ T-PBL.
内皮细胞表达黏附分子并释放游离形式（如可溶性内皮白细胞黏附分子 -1、可溶性血小板α颗粒膜蛋白 -140、可溶性细胞间黏附分子 -1和可溶性血管细胞黏附分子 -1）。与对照组相比，类风湿关节炎患者血清中这些可溶性黏附分子（SAM）水平显著升高。我们研究了这是否与循环细胞因子及外周血T淋巴细胞（T - PBL）亚群的变化有关。在健康受试者中，可溶性内皮白细胞黏附分子 -1与白细胞介素 -1β、白细胞介素 -1受体拮抗剂（IL -1RA）和白细胞介素 -6的血清水平相关，而可溶性血小板α颗粒膜蛋白 -140与白细胞介素 -8相关，可溶性血管细胞黏附分子 -1与白细胞介素 -7和白细胞介素 -8相关。因此，在对照组中，SAM水平与循环细胞因子之间就已存在关联。对血清中IgA和/或IgM类风湿因子（RF）水平低和高的类风湿关节炎患者分别进行了分析。他们具有不同的细胞因子谱且显示出不同的相关性。在RF水平低的患者中，可溶性血小板α颗粒膜蛋白 -140和可溶性血管细胞黏附分子 -1与白细胞介素 -1β相关，而可溶性细胞间黏附分子 -1与白细胞介素 -7和肿瘤坏死因子 -α相关。在RF水平高的患者中，可溶性内皮白细胞黏附分子 -1与白细胞介素 -1受体拮抗剂相关，可溶性血小板α颗粒膜蛋白 -140与多种细胞因子（如粒细胞 - 巨噬细胞集落刺激因子、巨噬细胞炎性蛋白 -1α和肿瘤坏死因子 -α）相关。此外，30%的患者出现淋巴细胞减少（淋巴细胞少于1000个/微升），20%（大多RF水平低）外周血T淋巴细胞中“致敏”的CD45RO +细胞水平降低。在对照组中，细胞因子（白细胞介素 -7、白细胞介素 -8和粒细胞 - 巨噬细胞集落刺激因子）而非SAM与较少的CD45RO + T - PBL相关。仅在RF水平低的患者中，可溶性血小板α颗粒膜蛋白 -140和可溶性内皮白细胞黏附分子 -1分别与“致敏性”CD4 +和CD8 + T - PBL的减少相关。在这类患者中，白细胞介素 -1β和粒细胞 - 巨噬细胞集落刺激因子也与较少的CD8 +、CD45RO + T - PBL相关。因此，特别是在RF水平低的患者中，可能由内皮细胞释放的SAM增加，可能反映了细胞因子诱导的血管内皮激活以及一些CD45RO + T - PBL的外渗。
