UP-REGULATION OF VLA-5 EXPRESSION DURING MONOCYTIC DIFFERENTIATION AND ITS ROLE IN NEGATIVE CONTROL OF THE SURVIVAL OF PERIPHERAL-BLOOD MONOCYTES

Interaction between fibronectin (FN) and very late activation Ag-5 (VL A-5) integrin was recently reported to be involved in apoptosis of hem atopoietic cells, In an effort to clarify the physiologic role of FN i n the regulation of biologic behavior of terminally differentiated hem atopoietic cells, we have examined the change of VLA-5 expression duri ng myeloid cell differentiation and its effects on monocytes and granu locytes. VLA-5 alpha mRNA was up-regulated during monocytic differenti ation, but not during granulocytic differentiation of HL-60 cells, Flo w cytometric and immunocytochemical analysis revealed that surface exp ression of VLA-5 was selectively increased upon monocytic differentiat ion and that it was strongly positive on peripheral blood monocytes, S usceptibility to FN-induced apoptosis was greatly increased upon monoc ytic differentiation, and it was almost completely abrogated by anti-V LA-5 Ab or RGD peptide, Similarly, FN could significantly enhance apop tosis of normal monocytes but not of granulocytes. Finally, we have sh own that anti-FN Ab could suppress spontaneous apoptosis of normal mon ocytes in culture and prolong their survival, These results suggest th at FN might play an important role in negative regulation of the survi val of monocytes through its interaction with VLA-5, which is selectiv ely up-regulated during monocytic differentiation.