The Antiproteolytic Activity of Serum I. the Nature and Expe~tm-f.ntal Variation of the Antiproteolytic

Hildebrandt (1893), Camus and Gley (1897), and Landsteiner (1900) were the first investigators to observe that normal serum markedly inhibits the action of trypsin and of yeast proteases. Opie (1905) and Jochmann (1908) demonstrated its ability to inhibit leucoprotease. Study of numerous species of animals (Launoy, 1919) showed antiproteolytic activity to be a constant property of mammalian and bird serum, but innumerable investigations have as yet led to little success in the identification of the substance or substances responsible for this property. The earliest, and still prevalent, theory of the origin of serum antiprotease is that it is a protective antibody formed by the body against proteolytic ferments emptied into the blood stream. This idea had its inception in the work of Achalme (1901) and Meyer (1909), who reported an increase in the antiproteolytiO activity of serum in response to intraperitoncal injection of trypsin into guinea pigs. This finding was refuted by some investigators (e.g., Bergeil and Schutze, 1905; Young, 1918), but confirmed and extended by Jochmann and Kantorowicz (1908), who demonstrated a rise in activity following subcutaneous injection of leucoprotease into rabbits, and who concluded from this that leucoprotease serves as the normal antigen in response to which antiprotcase is produced. Others (e.g., yon Bergmann and Gulecke, 1910) postulated that the pancreas rather than the leucocytes supplied the hypothetical protease antigen, and offered evidence that the antiproteolytic activity on the serum increases following implantation of the pancreas into the peritoneal cavity. This seemed to be supported by the work of Cobliner (1910), who showed that serum antiproteolytie activity decreases considerably following extirpation of the pancreas. Indirect evidence against the antibody theory has come from Landsteiner's re-