Antisense modulation of the ICAM-1 phenotype of a model human bone marrow stromal cell line.
Efficient stable gene transfer was achieved in a model human bone marrow stromal cell line, KM-102, using both Epstein-Barr virus and BK virus episomal expression vectors. Using this episomal expression system, effective overexpression and inhibition of ICAM-1 expression was achieved in stably transfected KM-102 cells by sense and antisense RNA gene transfer, respectively. Loss of surface ICAM-1 on antisense KM-102 transfectants did not significantly affect adhesion to LFA-1-bearing JY hematopoietic cells. However, KM-102 ICAM-1 overexpressors demonstrated enhanced binding (2.5-fold) to phorbol ester-treated, but not untreated, LFA-1-bearing JY cells. The increased binding could be blocked with anti-ICAM-1 antibodies. These findings suggest that while ICAM-1 is not required for basal adhesion between stromal and hematopoietic cells, stromal ICAM-1 may contribute to stromal:leukemic cellular interaction when bound to the phorbol ester-dependent high-avidity state of hematopoietic LFA-1.
Department of Pathology, Case Western Reserve University, Cleveland, Ohio, 44106, USA.
M C
MC
Weber
R K
RK
Groger
M L
ML
Tykocinski
D001739:BK Virus / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000166:cytology; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000502:physiology; D007938:Leukemia / Q000473:pathology; D008954:Models, Biological; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010641:Phenotype; D010957:Plasmids / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics / Q000494:pharmacology; D017154:Stromal Cells / Q000378:metabolism
D016376:Oligonucleotides, Antisense; D016372:RNA, Antisense; D018799:Intercellular Adhesion Molecule-1