Fong A M, Robinson L A, Steeber D A, Tedder T F, Yoshie O, Imai T, Patel D D
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Exp Med. 1998 Oct 19;188(8):1413-9. doi: 10.1084/jem.188.8.1413.
Leukocyte migration into sites of inflammation involves multiple molecular interactions between leukocytes and vascular endothelial cells, mediating sequential leukocyte capture, rolling, and firm adhesion. In this study, we tested the role of molecular interactions between fractalkine (FKN), a transmembrane mucin-chemokine hybrid molecule expressed on activated endothelium, and its receptor (CX3CR1) in leukocyte capture, firm adhesion, and activation under physiologic flow conditions. Immobilized FKN fusion proteins captured resting peripheral blood mononuclear cells at physiologic wall shear stresses and induced firm adhesion of resting monocytes, resting and interleukin (IL)-2-activated CD8(+) T lymphocytes and IL-2-activated NK cells. FKN also induced cell shape change in firmly adherent monocytes and IL-2-activated lymphocytes. CX3CR1-transfected K562 cells, but not control K562 cells, firmly adhered to FKN-expressing ECV-304 cells (ECV-FKN) and tumor necrosis factor alpha-activated human umbilical vein endothelial cells. This firm adhesion was not inhibited by pertussis toxin, EDTA/EGTA, or antiintegrin antibodies, indicating that the firm adhesion was integrin independent. In summary, FKN mediated the rapid capture, integrin-independent firm adhesion, and activation of circulating leukocytes under flow. Thus, FKN and CX3CR1 mediate a novel pathway for leukocyte trafficking.
白细胞迁移至炎症部位涉及白细胞与血管内皮细胞之间的多种分子相互作用，介导白细胞的依次捕获、滚动和牢固黏附。在本研究中，我们测试了在生理流动条件下，活化内皮细胞上表达的跨膜黏蛋白 - 趋化因子杂交分子—— fractalkine（FKN）与其受体（CX3CR1）之间的分子相互作用在白细胞捕获、牢固黏附和活化中的作用。固定化的FKN融合蛋白在生理壁面剪应力下捕获静息外周血单核细胞，并诱导静息单核细胞、静息和白细胞介素（IL）-2激活的CD8(+) T淋巴细胞以及IL-2激活的NK细胞的牢固黏附。FKN还诱导牢固黏附的单核细胞和IL-2激活的淋巴细胞发生细胞形态改变。CX3CR1转染的K562细胞，而非对照K562细胞，能牢固黏附于表达FKN的ECV-304细胞（ECV-FKN）和肿瘤坏死因子α激活的人脐静脉内皮细胞。这种牢固黏附不受百日咳毒素、EDTA/EGTA或抗整合素抗体的抑制，表明该牢固黏附不依赖整合素。总之，FKN在流动状态下介导循环白细胞的快速捕获、不依赖整合素的牢固黏附和活化。因此，FKN和CX3CR1介导了一种新的白细胞迁移途径。
