Papadaki H A, Eliopoulos G D
Department of Hematology of the University of Crete School of Medicine, University Hospital of Heraklion, Greece.
Ann Hematol. 1998 Oct;77(4):153-9. doi: 10.1007/s002770050433.
The present study was designed to investigate the hypothesis that selective loss of peripheral blood CD45RO+ T lymphocytes in patients with chronic idiopathic neutropenia of adults (CINA), previously reported from our laboratory, may be due to enhanced extravasation into the tissues. Serum levels of endothelial cell-derived soluble cell adhesion molecules (sELAM, sICAM and sVCAM), usually used as indicators of endothelial cell activation, were measured in 73 CINA patients and 32 healthy volunteers using a micro-ELISA method. We found that patients had markedly elevated concentrations of all three soluble cell adhesion molecules studied compared to the controls, and serum levels of sELAM, sICAM and, more importantly, sVCAM correlated inversely with the numbers of both CD4+/CD45RO+ and CD8+/CD45RO+ T cell subsets. Using a micro-ELISA method, we also measured serum levels of two endothelial cell activators, interleukin (IL)-1beta and TNF-alpha, and found that CINA patients had significantly higher cytokine concentrations than control subjects. Serum levels of IL-1beta and TNF-alpha correlated positively with the values of all three soluble cell adhesion molecules and inversely with the numbers of CD4+/CD45RO+ and CD8+/CD45RO+ T cell subsets. Moreover, we measured serum levels of the chemokine RANTES by a micro-ELISA technique and found that CINA patients also had elevated concentrations of the molecule compared to controls. Serum RANTES correlated positively with IL-1beta, TNF-alpha, sICAM, sVCAM and sELAM and inversely with the numbers of both CD4+/CD45RO+ and CD8+/CD45RO+ T cell subsets. These findings strongly suggest that CINA patients have an activated endothelium to which CD45RA+ and CD45RO+ T cells tether and roll, but firm adhesion and transendothelial migration are restricted to CD45RO+ T cell subsets, as endothelial VCAM-1 interacts with the vascular leukocyte adhesion molecule-4 (VLA-4) constitutively expressed on CD45RO+ but not on CD45RA+ T cells. Subsequent subendothelial and tissue migration of CD45RO+ T cells may be facilitated by the chemokine RANTES, which acts mainly on CD45RO+ T cells. We concluded that selective loss of peripheral blood CD45RO+ T lymphocytes in CINA patients is probably due, at least in part, to enhanced extravasation of both CD4+/CD45RO+ and CD8+/CD45RO+ T cell subsets into the tissues.
本研究旨在探讨一个假说，即我们实验室之前报道的成年慢性特发性中性粒细胞减少症（CINA）患者外周血CD45RO⁺ T淋巴细胞的选择性丢失，可能是由于向组织内的渗出增加所致。采用微量酶联免疫吸附测定法，对73例CINA患者和32名健康志愿者检测了通常用作内皮细胞活化指标的内皮细胞衍生可溶性细胞黏附分子（sELAM、sICAM和sVCAM）的血清水平。我们发现，与对照组相比，患者所研究的所有三种可溶性细胞黏附分子的浓度均显著升高，且sELAM、sICAM，更重要的是sVCAM的血清水平与CD4⁺/CD45RO⁺和CD8⁺/CD45RO⁺ T细胞亚群的数量呈负相关。采用微量酶联免疫吸附测定法，我们还检测了两种内皮细胞激活剂白细胞介素（IL）-1β和肿瘤坏死因子-α的血清水平，发现CINA患者的细胞因子浓度显著高于对照受试者。IL-1β和肿瘤坏死因子-α的血清水平与所有三种可溶性细胞黏附分子的值呈正相关，与CD4⁺/CD45RO⁺和CD8⁺/CD45RO⁺ T细胞亚群的数量呈负相关。此外，我们采用微量酶联免疫吸附技术检测了趋化因子RANTES的血清水平，发现与对照组相比，CINA患者该分子的浓度也升高。血清RANTES与IL-1β、肿瘤坏死因子-α、sICAM、sVCAM和sELAM呈正相关，与CD4⁺/CD45RO⁺和CD8⁺/CD45RO⁺ T细胞亚群的数量呈负相关。这些发现有力地表明，CINA患者存在活化的内皮，CD45RA⁺和CD45RO⁺ T细胞可与之栓系和滚动，但牢固黏附和跨内皮迁移仅限于CD45RO⁺ T细胞亚群，因为内皮血管细胞黏附分子-1（VCAM-1）与CD45RO⁺而非CD45RA⁺ T细胞上组成性表达的血管白细胞黏附分子-4（VLA-4）相互作用。趋化因子RANTES可能促进CD45RO⁺ T细胞随后的内皮下和组织迁移，RANTES主要作用于CD45RO⁺ T细胞。我们得出结论，CINA患者外周血CD45RO⁺ T淋巴细胞的选择性丢失可能至少部分是由于CD4⁺/CD45RO⁺和CD8⁺/CD45RO⁺ T细胞亚群向组织内的渗出增加所致。
