Cross-linking of CD54 on Burkitt lymphoma cell line Raji and Ramos induces FasL expression by reactive oxygen species and apoptosis of adjacent cells in Fas/FasL interaction.
CD54 is a cell surface adhesive glycoprotein, which is expressed in most cells. Interaction between CD54 and its ligands is involved in several cellular events including activation, proliferation, and cell death and also cell-to-cell adhesion. In the present study, we found that cross-linking of CD54 on Burkitt lymphoma cell lines, Raji and Ramos, induced apoptosis. We investigated that cross-linking of CD54 on Raji and Ramos using immobilized anti-CD54 mAb (clone 6.5B5) leads to apoptosis. CD54-induced apoptosis took place in association with an increase of intracellular reactive oxygen species (ROS) and a loss of the mitochondrial membrane potential and also the activation of caspases 3 and 9, resulting in the degradation of the proteolytic poly (ADP-ribose) polymerase. Pretreatment of each N-acetyl cystein and N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (a broad caspase inhibitor) blocked apoptosis. Cross-linking of CD54 immediately induced expression of fasL, which was inhibited by pretreatment of N-acetyl cystein. NOK-1 (antagonistic anti-fasL), ZB4 (antagonistic anti-fas), and N-benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethylketon (caspase 8 inhibitor) effectively rescued cells from apoptosis via adjacent fas-fasL interaction but did not block ROS generation. Taken together, it is concluded that engagement of CD54 on B lymphoma cell lines by anti-CD54 mAb may trigger fasL expression through ROS generation and may subsequently induce apoptosis in adjacent fas-fasL interaction.
Kim
Yeong Seok
YS
Department of Anatomy and Research Center for Women's Disease, Inje University Busan Paik Hospital, Busan, Republic of Korea.
Park
Ga Bin
GB
Song
Hyun Keun
HK
Hur
Indo
I
Lee
Hyun-Kyung
HK
Kang
Jae Seung
JS
Hahm
Eunsil
E
Lee
Wang Jae
WJ
Hur
Dae Young
DY
D017209:Apoptosis; D002051:Burkitt Lymphoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D017382:Reactive Oxygen Species; D019014:fas Receptor; D018799:Intercellular Adhesion Molecule-1; D020169:Caspases