Monokine-induced synthesis of serum amyloid A protein by hepatocytes

Infection or inflammation triggers the rapid appearance in the blood of a group of proteins known as acute phase reactants¹. Serum amyloid A protein (SAA) is an acute phase protein which is believed to be the precursor for the secondary amyloid fibril protein, known previously as amyloid of unknown origin, and now as amyloid A protein (AA). The site of synthesis of SAA has been controversial, with previous evidence suggesting that AA related proteins arise in liver^2-4, connective tissues⁵, polymorphonuclear neutrophil leukocytes⁶ and spleen⁷. However, in none of these systems could SAA synthesis be induced in vitro and the evidence rested on studies of tissues or cells arising from pre-stimulated animals. Our aim in the present studies was to prove that the liver is capable of SAA production and to identify the specific cell responsible for synthesis. The experiments demonstrate that SAA is synthesized in the liver by hepatocytes. In addition, colchicine, currently used for the treatment of amyloidosis, blocks the secretion of SAA from the hepatocyte, as has been shown for another acute phase reactant, C-reactive protein⁸.