The site of synthesis and functions of acute phase plasma proteins: Close relation-ship with the reticulo-endothelial system

The evidence that the acute phase glycoproteins of plasma are synthesized by the liver parenchymal cells is critically examined, and is found to be inconclusive. Some evidence is cited which favors the reticulo-endothelial system (RES) in general, and Kupffer cells in particular, as the site of synthesis of these proteins: 1. The entire RES contains non-glycogenic periodic acid Schiff-positive substances. 2. The diseases which affect glycoprotein levels are also known to affect the function of the RES. 3. When the animal is subjected to stress, the RES function is initially depressed and then stimulated. A similar biphasic behavior is shown by plasma glycoprotein levels. 4. Adrenal cortico-steriods are the major regulators of the RES function and of the synthesis of acute phase proteins. Moreover, both are stimulated at low concentrations, and depressed at high concentrations of the hormone. Some of the glycoproteins of the acute phase (prothrombin, the third component of complement, haptoglobin, transferrin and ceruloplasmin) have defense-related functions. The others seem to participate in phenomena like detoxification, promotion of phagocytosis, wound healing, prevention of tissue injury by lysosomal enzymes, prevention of trauma and recovery from inflammation. It is proposed that the acute phase proteins, together with antibodies, form major components of the defense system, and the RES attempts to deal with injury by mobilization of increased amounts of these substances.