Synthesis and Secretion of a Mitogenic Protein by Macrophages: Description of a Superinduction Phenomenon

We have examined the biosynthesis and fate of the mitogenic protein (MP)2 made by macrophages. This mitogenic protein was assayed by its stimulation of DNA synthesis of thymocytes. Macrophages freshly harvested from the peritoneal cavity did not contain MP in the cell. The MP, however, rapidly appeared in the cell, reaching maximum amount by 1 to 2 hr, maintaining its concentration up to about 6 hr, and then disappearing. The disappearance of MP did not correlate with its secretion into the medium. The elaboration of MP stimulated by contact with the dish was inhibited by cycloheximide. Exposure of the cells to inhibitors of protein synthesis after 1 to 2 hr of culture at a time when the MP was already made produced a striking increase in secretion. The MP inside the cell did not appear to decay in the presence of cycloheximide. This result thus represents another example of superinduction. The intracellular fate of MP appears to be under the regulation of a control protein.