Terui Y, Furukawa Y, Sakai T, Kikuchi J, Sugahara H, Kanakura Y, Kitagawa S, Miura Y
Institute of Hematology, Jichi Medical School, Tochigi, Japan.
J Immunol. 1996 Mar 1;156(5):1981-8.
Interaction between fibronectin (FN) and very late activation Ag-5 (VLA-5) integrin was recently reported to be involved in apoptosis of hematopoietic cells. In an effort to clarify the physiologic role of FN in the regulation of biologic behavior of terminally differentiated hematopoietic cells, we have examined the change of VLA-5 expression during myeloid cell differentiation and its effects on monocytes and granulocytes. VLA-5 alpha mRNA was up-regulated during monocytic differentiation, but not during granulocytic differentiation of HL-60 cells. Flow cytometric and immunocytochemical analysis revealed that surface expression of VLA-5 was selectively increased upon monocytic differentiation and that it was strongly positive on peripheral blood monocytes. Susceptibility to FN-induced apoptosis was greatly increased upon monocytic differentiation, and it was almost completely abrogated by anti-VLA-5 Ab or RGD peptide. Similarly, FN could significantly enhance apoptosis of normal monocytes but not of granulocytes. Finally, we have shown that anti-FN Ab could suppress spontaneous apoptosis of normal monocytes in culture and prolong their survival. These results suggest that FN might play an important role in negative regulation of the survival of monocytes through its interaction with VLA-5, which is selectively up-regulated during monocytic differentiation.
最近有报道称，纤连蛋白（FN）与极晚期活化抗原-5（VLA-5）整合素之间的相互作用参与造血细胞的凋亡。为了阐明FN在终末分化造血细胞生物学行为调控中的生理作用，我们研究了髓系细胞分化过程中VLA-5表达的变化及其对单核细胞和粒细胞的影响。在HL-60细胞单核细胞分化过程中，VLA-5α mRNA上调，但在粒细胞分化过程中未上调。流式细胞术和免疫细胞化学分析显示，VLA-5的表面表达在单核细胞分化时选择性增加，并且在外周血单核细胞上呈强阳性。单核细胞分化后，对FN诱导的凋亡敏感性大大增加，抗VLA-5抗体或RGD肽几乎完全消除了这种敏感性。同样，FN可显著增强正常单核细胞的凋亡，但对粒细胞无此作用。最后，我们发现抗FN抗体可抑制培养的正常单核细胞的自发凋亡并延长其存活时间。这些结果表明，FN可能通过与VLA-5相互作用在单核细胞存活的负调控中发挥重要作用，VLA-5在单核细胞分化过程中选择性上调。
