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Hepatocytes express blood coagulation factor XII (Hageman factor)
E M Gordon1, C A Gallagher, T R Johnson
1Division of Hematology-Oncology, Childrens Hospital of Los Angeles, CA 90027.
The Journal of Laboratory and Clinical Medicine
|April 1, 1990
Summary
Primary rat hepatocytes were identified as the specific cells responsible for synthesizing blood coagulation factor XII (Hageman factor). These liver cells actively transcribe, produce, and secrete this crucial clotting protein.
Area of Science:
- Biochemistry
- Cell Biology
- Hematology
Background:
- The liver is known to synthesize blood coagulation factor XII (Hageman factor).
- The precise cell type responsible for factor XII expression within the liver remained unidentified prior to this study.
Purpose of the Study:
- To identify the specific cell type responsible for factor XII synthesis in the liver.
- To investigate the transcription, de novo synthesis, and secretion of factor XII by primary rat hepatocytes.
Main Methods:
- Primary rat hepatocytes were cultured in serum-free medium.
- RNA blot hybridization was performed using a 32P-labeled human factor XII complementary DNA probe.
- Factor XII synthesis and secretion were assessed using radiolabeled leucine and cycloheximide inhibition.
- Western immunoblotting was used to compare secreted factor XII with authentic plasma factor XII.
Main Results:
- Hepatocyte cultures showed a 2.4 kilobase messenger RNA transcript for factor XII.
- Hepatocytes secreted de novo synthesized, radiolabeled factor XII.
- Immunoreactive and clotting activity of factor XII increased in hepatocyte cultures over 24 hours.
- Cycloheximide treatment inhibited factor XII accumulation.
- Secreted factor XII from hepatocytes matched authentic rat plasma factor XII in molecular weight.
Conclusions:
- Primary rat hepatocytes are confirmed to transcribe, synthesize, and secrete authentic factor XII.
- This study identifies hepatocytes as the specific cell type responsible for factor XII production in the liver.
- These findings contribute to understanding the hepatic regulation of the coagulation cascade.