NEUTROPHILS AS A SOURCE OF PUTATIVE RESTRICTION PROTEASES - DEGRADATION OF MAMMALIAN AND YEAST PROTEINS MONITORED BY 2-DIMENSIONAL GEL-ELECTROPHORESIS

We have compared the ability of intact neutrophils to degrade a comple x substrate of proteins from mammalian and yeast origin. The substrate was obtained by biosynthetic labeling, and subsequent lysis of K562 c ells (leukemic cell line) and of yeast culture. The mammalian substrat e consisted of 619 and the yeast substrate of 185 different polypeptid es, as visualized and represented on two-dimensional gel patterns. Upo n incubation of the mammalian substrate with neutrophils, the bulk of spots disappeared so rapidly that after 240 min of incubation only 21 spots were detectable. Just one spot remained unaltered in its intensi ty throughout the whole period of incubation. About 440 spot reveal a t(1/2) shorter than 8 min. Yeast substrate is represented by a smaller number of the starting polypeptides (185) from which 55 spots ''survi ve'' the neutrophil treatment. About 30 spots have a t(1/2) shorter th an 8 min. We conclude that neutrophils are equipped with a potent prot eolytic apparatus, and this is capable of eliminating various proteins in a highly efficient manner. The system is much less effective in el iminating proteins from distant species, like yeast. Although the cell s governing and regulating the immune system are clearly of lymphoid o rigin, it might well be that the preimmune task of eliminating self an tigens in a manner as predicted in the restriction protease hypothesis is performed by neutrophils.