During the acute inflammatory reaction (AIR), the plasma concentration of several plasma proteins, including fibrinogen, is increased as a result of enhanced production by the liver. Whether this increased production influences the production of the other plasma proteins at the single hepatocyte level is not known. Accordingly, we simultaneously measured albumin and fibrinogen secretion by single hepatocytes isolated from normal rats and from rats sacrificed 24 hr after a turpentine-induced AIR, using an hemolytic plaque test. In normal rats, 74, 82, and 98% of the hepatocytes were detected as secreting albumin, after 1, 2, and 4 hr of incubation, respectively. Simultaneously, 0, 32, and 62% of the hepatocytes were detected as secreting fibrinogen at the same incubation times. For secretion of both proteins, a significant correlation was established between the diameter of a plaque-forming hepatocyte and its hemolytic plaque. In rats with AIR, the formation of hemolytic plaques detecting albumin secretion was slowed down compared to normal rats, since only 0, 36, and 78% of the hepatocytes were forming hemolytic plaques after 1, 2, and 4 hr of incubation, respectively. Simultaneously, the formation of hemolytic plaques detecting fibrinogen secretion was increased compared to normal rats, since at the same incubation times, 52, 78, and 93% of the hepatocytes formed hemolytic plaques. A significant correlation between the diameter of a plaque-forming hepatocyte and its hemolytic plaque was still maintained for both protein secretion.
These results demonstrate that during the AIR enhanced fibrinogen production is the result of an increased secretion rate per cell, and decreased albumin secretion is the result of a lowered secretion rate per cell, generalized for all hepatocytes. These data strongly suggest that there is a reciprocal modulation of fibrinogen and albumin secretion at the single hepatocyte level during the AIR.