Anti-glycophorin C induces mitochondrial membrane depolarization and a loss of extracellular regulated kinase 1/2 protein kinase activity that is prevented by pretreatment with cytochalasin D: implications for hemolytic disease of the fetus and newborn caused by anti-Ge3

作者：Micieli Jonathan A; Wang Duncheng; Denomme Gregory A^*

来源：Transfusion, 2010, 50(8): 1761-1765.

DOI：10.1111/j.1537-2995.2010.02640.x

BACKGROUND: Anti-glycophorin C (G PC), blood group antibodies of which cause hemolytic disease of the fetus and newborn (HDFN), is a potent inhibitor of erythroid progenitor cell growth. The cellular mechanism for growth inhibition has not been characterized.
STUDY DESIGN AND METHODS: K562 cells were incubated in the presence of either anti-GPO, an immunoglobulin G isotype control, an inhibitor of actin polymerization called cytochalasin D with anti-GPO, or cytochalasin D alone. The JC-1 cationic dye was used to detect mitochondrial depolarization and the activity of the mitogen-activated protein kinases was assessed by Western blotting.
RESULTS: Anti-GPC inhibits the activity of extracellular regulated kinase (ERK)1/2 within 10 minutes but does not alter the activity of p38 or c-Jun N-terminal kinase. After 24 hours there was a significant loss of mitochondrial membrane potential compared to isotype control treated cells. Both the ERK1/2 inhibition and the loss of mitochondrial potential were prevented by pretreatment with cytochalasin D.
CONCLUSION: A cell surface antibody can cause anemia by altering the signaling pathways in erythroid cells by promoting depolarization of mitochondria via cytoskeletal rearrangement. The observation that neonates with anti-GPO HDFN are unresponsive to erythropoietin can be explained by the antibody inhibiting a protein kinase through which this hematopoietic growth factor achieves its effects.

• 出版日期2010-8