The Expression and Regulation of ADAMTS13 in Hematopoietic System.

Background and Objective In 2001, VWF-cleaving protease was identified as ADAMTS13, a member of the ADAMTS family of metalloprotease. ADAMTS13 is now found as the mainly cleaving enzyme of VWF in plasma. It is synthesized predominantly in the liver, although variable expression has been observed in other issues including bone marrow. Although ADAMTS13 was detected only in platelet, not other blood cells, it is unsure what kind of situations would be when we come to immature hematopoietic cells. So we investigated ADAMTS13 in cell lines such as M07e, MEG01, HEL, k562, SHI-1, NB4, MR2 etc., to see if there is ADAMTS13 produced by blast cell of megakaryocyte and granulocyte and so on.

Methods We determined ADAMTS13 cDNA by RT-PCR and ADAMTS13 expression by flow cytometry and western blotting with some mono-clone antibodies against ADAMTS13. During all those test, we use human platelets as positive control.

Results ADAMTS13 was detectable in all those cell lines. It was highly expressed in M07e and MR2, and a bit lower in MEG01 and HEL, and much lower in k562, SHI-1 and NB4. While to our surprise, ADAMTS13 was up-regulated when NB4 was treated by 1μmol/L ATRA for 72 hours. When CD11b was rising from 21% up to 95% in NB4 after treatment, expression of ADAMTS13 followed by from 24% to 80%.

Conclusions Now we know what kinds of cells may express ADAMTS13 in bone marrow, the major part of it is localized in megakaryocyte. ADAMTS13 can highly expressed in NB4 after treatment with ARTA.