Human endothelial cells synthesize and release ADAMTS-13

Abstract

Hepatic stellate cells have been considered to be a primary source for human plasma ADAMTS-13, the von Willebrand factor (VWF)-cleaving metalloprotease. In this study, ADAMTS-13 antigen was detected by immunofluorescence in both venous (HUVECs) and arterial endothelial cells (HUAECs) using both polyclonal antibodies made against peptides found in various domains of human ADAMTS-13, as well as by a monoclonal antibody against the ADAMTS-13 metalloprotease domain. ADAMTS-13 antigen had an intra-cellular distribution in endothelial cells distinct from the Weibel-Palade body location of VWF, and was released from the cells during 48 h in culture. The mRNA for ADAMTS13 was detected in HUVECs and HUAECs using reverse transcription-polymerase chain reaction (RT-PCR), indicating that the enzyme is synthesized in these cells. The ADAMTS-13 protein was immunoprecipitated from HUVECs and had an approximate M(r) of 170 kDa, similar to the molecular mass of recombinant ADAMTS-13. The ADAMTS-13 in HUVEC and HUAEC lysates had enzymatic activity using both static and flow assays. We conclude that ADAMTS-13 is synthesized in human endothelial cells, and released constitutively. The vast number of endothelial cells in the body may be an important source of ADAMTS-13.

Prediction of Hepatocellular Carcinoma Development by Plasma ADAMTS13 in Chronic Hepatitis B and C

“…These results indicate that hepatic stellate cells play an important role in the regulation of plasma ADAMTS13 activity, although other sources of ADAMTS13 were reported (14)(15)(16).…”

Biologically active ADAMTS13 is expressed in renal tubular epithelial cells

“…An ADAMTS13 band at 170 kD has previously been described in endothelial cell lysates [25]. The slightly lower band detected in the medium may represent a breakdown product.…”

Thrombotic Thrombocytopenic Purpura: A Thrombotic Disorder Caused by ADAMTS13 Deficiency

“…In the liver, ADAMTS13 is expressed primarily in the vitamin A-enriched stellate cells [9;10]. ADAMTS13 may also be expressed in platelets and endothelial cells [11][12][13].…”