Weber M C, Groger R K, Tykocinski M L
Department of Pathology, Case Western Reserve University, Cleveland, Ohio, 44106, USA.
Exp Cell Res. 1998 Oct 10;244(1):239-48. doi: 10.1006/excr.1998.4192.
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.
利用爱泼斯坦-巴尔病毒和BK病毒附加型表达载体，在人骨髓基质细胞系模型KM-102中实现了高效稳定的基因转移。使用这种附加型表达系统，通过正义和反义RNA基因转移，在稳定转染的KM-102细胞中分别实现了ICAM-1表达的有效过表达和抑制。反义KM-102转染子表面ICAM-1的缺失并未显著影响其与携带LFA-1的JY造血细胞的黏附。然而，KM-102 ICAM-1过表达细胞对佛波酯处理而非未处理的携带LFA-1的JY细胞表现出增强的结合（2.5倍）。这种增加的结合可以被抗ICAM-1抗体阻断。这些发现表明，虽然ICAM-1对于基质细胞和造血细胞之间的基础黏附不是必需的，但当基质ICAM-1与造血LFA-1的佛波酯依赖性高亲和力状态结合时，可能有助于基质细胞与白血病细胞的相互作用。
