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 (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.
Terui
Y
Y
Institute of Hematology, Jichi Medical School, Tochigi, Japan.
Furukawa
Y
Y
Sakai
T
T
Kikuchi
J
J
Sugahara
H
H
Kanakura
Y
Y
Kitagawa
S
S
Miura
Y
Y
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001483:Base Sequence; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D005353:Fibronectins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology*
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D017469:Receptors, Fibronectin