Production of macrophage activation factors by tryptic cleavage of calf serum proteins

Trypsin, when added to a bioassay for tumoricidal macrophages, produced killing of tumor cells. Trypsin cleaved fetal calf serum proteins to produce a protein fragment that activated macrophages to lyse tumor cells. Diisopropyl fluorophosphate-inhibited trypsin did not produce tumoricidal macrophages either by direct action on the macrophage or by action on serum proteins. The macrophage activation factors produced from serum proteins were fractionated into molecular weight ranges of 150,000, 68,000, and 30,000-5000. The effects of neutral proteinases and proteinase inhibitors on the ability of macrophages to lyse tumor cells is discussed.