Howells G L, Macey M, Murrell A M, Green A R, Curtis M A, Stone S R
Department of Oral Pathology, London Hospital Medical College (LHMC).
Br J Haematol. 1994 Oct;88(2):383-8. doi: 10.1111/j.1365-2141.1994.tb05034.x.
It has recently been shown that peripheral blood NK-cells and a fraction of T-cells which co-express CD16 and either CD56 or CD57 express the platelet type thrombin receptor. Large granular lymphocytes exhibit a T- or NK-cell phenotype, and therefore these results raise the possibility that thrombin and its receptor may be involved in the biology of large granular lymphocytes in health and disease. It is difficult, however, to perform functional studies using normal blood as a source of large granular lymphocytes, because the small fraction of large granular lymphocytes cannot be separated from other lymphocytes in numbers sufficient for most in vitro experiments. Therefore patients with large granular lymphocyte proliferative disorders have been screened in order to identify a population of cells enriched in large granular lymphocytes that express the thrombin receptor. Expression of the receptor was analysed in polyclonal and clonal large granular lymphocyte proliferative disorders. Using flow cytometry, it was found that the proportion of thrombin receptor positive large granular lymphocytes varied from 3% to 86%. Northern analysis indicated a high level of expression of mRNA in a clonal expansion of large granular lymphocytes that stained positively for the receptor by flow cytometry. Thrombin was found to act as a chemotactic stimulus for large granular lymphocytes from a polyclonal expansion with high numbers of thrombin receptor positive cells. At an optimal concentration of 10(-9) M the chemotactic response to thrombin was roughly equivalent to that obtained with the potent chemoattractant 1-oleoyl 2-acetyl glycerol. These findings suggest that thrombin may play a role in the recruitment of large granular lymphocytes in sites of inflammation.
最近研究表明，外周血自然杀伤细胞（NK 细胞）以及一部分共表达 CD16 和 CD56 或 CD57 的 T 细胞表达血小板型凝血酶受体。大颗粒淋巴细胞表现出 T 细胞或 NK 细胞表型，因此这些结果提示凝血酶及其受体可能在健康和疾病状态下大颗粒淋巴细胞的生物学过程中发挥作用。然而，使用正常血液作为大颗粒淋巴细胞的来源进行功能研究存在困难，因为大颗粒淋巴细胞的比例较小，无法从其他淋巴细胞中分离出足够数量用于大多数体外实验。因此，对大颗粒淋巴细胞增殖性疾病患者进行了筛查，以鉴定富含表达凝血酶受体的大颗粒淋巴细胞的细胞群体。分析了多克隆和克隆性大颗粒淋巴细胞增殖性疾病中该受体的表达情况。通过流式细胞术发现，凝血酶受体阳性的大颗粒淋巴细胞比例在 3%至 86%之间。Northern 分析表明，在流式细胞术检测中受体染色呈阳性的大颗粒淋巴细胞克隆性扩增中，mRNA 表达水平较高。发现凝血酶对来自多克隆扩增且含有大量凝血酶受体阳性细胞的大颗粒淋巴细胞具有趋化刺激作用。在最佳浓度 10⁻⁹ M 时，对凝血酶的趋化反应大致相当于用强效趋化剂 1-油酰基-2-乙酰甘油所获得的反应。这些发现提示凝血酶可能在炎症部位大颗粒淋巴细胞的募集过程中发挥作用。
