52 C. DE DUVE 



spectrum of activity which encompasses many important cell 

 constituents. They are retained within the lysosomes by a 

 membrane which effectively prevents their access to external 

 substrates, and they are released in soluble and fully active 

 form by all treatments which damage this membrane. Present 

 indications are that lysosomes may represent only a very 

 small fraction of the cell content and correspond with some 

 type of dense bodies occasionally seen in tissue sections. 



The most obvious implication of these findings is a negative 

 one. They show that the soluble acid hydrolases are separated 

 from most other cell constituents by a barrier which prevents 

 them from acting on those constituents. In the present case, 

 this negative aspect of segregation appears to be particularly 

 important, since it concerns a group of enzymes which might 

 very well cause considerable damage and even death if they 

 were free to act within the whole cell. We have, in fact, been 

 able to demonstrate that lysosomes release their enzymes very 

 rapidly in necrotizing tissue. 



The positive aspect of segregation is provided by the nature 

 of the enzymes which are found to be associated and to form, 

 therefore, what may be assumed to be a true physiological 

 system. Association is more difficult to demonstrate un- 

 equivocally than separation, and we are not entirely certain 

 that the lysosomal enzymes are all grouped together within a 

 single type of particle. However, the bulk of the evidence is 

 compatible with such a possibility and authorizes some 

 speculation on the significance of the suspected association. 

 This has led to the consideration that the only process in 

 which the lysosomal enzymes could possibly be involved 

 jointly is one of digestion of objects of complex chemical 

 composition. Since liver lysosomes do not appear in bile and 

 since similar particles exist in tissues other than digestive 

 glands, the digestive phenomena with which they are con- 

 cerned are taken to be intracellular and linked with engulfing 

 processes such as phagocytosis, athrocytosis and pinocytosis. 

 Some measure of support for this hypothesis has been furn- 

 ished by the work of Straus (1956, 1957) on kidney lysosomes. 



