Alon R, Rossiter H, Wang X, Springer T A, Kupper T S
Department of Pathology, Brigham and Womem's Hospital, Harvard Medical School Boston, Massachusetts 02115.
J Cell Biol. 1994 Dec;127(5):1485-95. doi: 10.1083/jcb.127.5.1485.
Memory T lymphocytes extravasate at sites of inflammation, but the mechanisms employed by these cells to initiate contact and tethering with endothelium are incompletely understood. An important part of leukocyte extravasation is the initiation of rolling adhesions on endothelial selectins; such events have been studied in monocytes and neutrophils but not lymphocytes. In this study, the potential of T lymphocytes to adhere and roll on endothelial selectins in vitro was investigated. We demonstrate that T cells can form tethers and rolling adhesions on P selectin and E selectin under physiologic flow conditions. Tethering and rolling on P selectin was independent of cell-surface cutaneous lymphocyte antigen (CLA) expression, which correlated strictly with the capacity of T cells to form rolling adhesions under flow on E selectin. T cell tethering to P selectin was abolished by selective removal of cell surface sialomucins by a P. haemolytica O-glycoprotease, while cutaneous lymphocyte antigen expression was unaffected. A sialomucin molecule identical or closely related to P selectin glycoprotein ligand-1 (PSGL-1), the major P selectin ligand on neutrophils and HL-60 cells, appears to be a major T cell ligand for P selectin. P selectin glycoprotein ligand-1 does not appear to support T cell rolling on E selectin. In turn, E selectin ligands do not appear to be associated with sialomucins. These data demonstrate the presence of structurally distinct ligands for P or E selectins on T cells, provide evidence that both ligands can be coexpressed on a single T cell, and mediate tethering and rolling on the respective selectins in a mutually exclusive fashion.
记忆性T淋巴细胞在炎症部位渗出,但这些细胞与内皮细胞起始接触和黏附的机制尚未完全明了。白细胞渗出的一个重要部分是在内皮选择素上起始滚动黏附;此类事件已在单核细胞和中性粒细胞中进行了研究,但未在淋巴细胞中开展研究。在本研究中,我们调查了T淋巴细胞在体外黏附并在内皮选择素上滚动的可能性。我们证明,在生理流动条件下,T细胞可在P选择素和E选择素上形成黏丝和滚动黏附。在P选择素上的黏丝形成和滚动与细胞表面皮肤淋巴细胞抗原(CLA)表达无关,而CLA表达与T细胞在流动状态下在E选择素上形成滚动黏附的能力严格相关。通过溶血巴氏杆菌O-糖蛋白酶选择性去除细胞表面唾液黏蛋白可消除T细胞与P选择素的黏附,而皮肤淋巴细胞抗原表达不受影响。一种与中性粒细胞和HL-60细胞上主要的P选择素配体P选择素糖蛋白配体-1(PSGL-1)相同或密切相关的唾液黏蛋白分子似乎是T细胞与P选择素结合的主要配体。P选择素糖蛋白配体-1似乎不支持T细胞在E选择素上滚动。反过来,E选择素配体似乎与唾液黏蛋白无关。这些数据证明T细胞上存在P或E选择素在结构上不同的配体,提供了两种配体可在单个T细胞上共表达的证据,并以相互排斥的方式介导在各自选择素上的黏丝形成和滚动。