Synchronous increase of four acute phase proteins synthesized by the same hepatocytes during the inflammatory reaction: a combined biochemical and morphologic kinetics study in the rat.

The hepatic synthesis of four "acute phase reactants" (APR), i.e., fibrinogen, alpha 1-acid glycoprotein, alpha 2-macroglobulin, and haptoglobin has been investigated in rats suffering from turpentine-induced inflammation. To follow the change in the rates of synthesis of the four APR, their concentrations were measured by immunonephelemetry in both the plasma and the hepatic microsomal fraction at various times after injury. A synchronous increase in the concentrations of these four proteins was observed in the liver (maximum 24 hours) as well as in the plasma (maximum 40 hours) of the same animals. In parallel, the site of their synthesis was localized in liver sections by light and electron microscopy using direct immunoperoxidase labeling. Of the liver cells, only the hepatocytes were labeled. In the early period of the inflammatory reaction (10 to 16 hours), synthesizing cells were detected principally in the periportal zone, but later (24 hours), the labeled area was extended to nearly the entire hepatic lobule. When serial sections of liver were examined at that time, the same cells were found to contain simultaneously the four APR. Within the cells examined by electron microscopy, the four proteins were localized in the secretory pathway, i.e., rough and smooth endoplasmic reticulum, Golgi apparatus, and secretory vacuoles. Therefore, we conclude that: (1) the experimental inflammatory reaction induces a synchronous increase in the synthesis of four APR by the liver; (2) this increased synthesis apparently results from an increased number of synthesizing hepatocytes; (3) these cells have a preferential periportal localization; and (4) individual hepatocytes are not specialized in the synthesis of a single plasma protein.