LYSOSOMES, A NEW GROUP OF CYTOPLASMIC PARTICLES I49 



tionship between lysosomes and pinocytosis can be clearly appreciated. At present, 

 the evidence that such a relationship exists appears fairly convincing and it may 

 be useful to keep in mind, pending further information, that the biochemical con- 

 cept of lysosomes (rig. i) may possibly cover several biologically and morphologi- 

 cally distinct entities, namely: /) zymogen-like granules containing newly syn- 

 thesized enzymes; 2) pinocytosis vacuoles at various stages of their evolution; 

 j) residual bodies, containing only the remnants of the digested material. 



The polymorphism of the dense bodies, the presence or absence of iron particles 

 within their matrix, as well as the heterogeneity of lysosomes with respect to size, 

 enzyme content and sensitivity to osmotic disruption, are perhaps related to this 

 diversity. 



The above considerations also inspire due caution with regard to the interpreta- 

 tion to be given to the free activities of lysosomal enzymes found in homo- 

 genates. As will be shown below, we have obtained evidence that high free ac- 

 tivities may have a pathological significance and be associated with necrosis. The 

 observations of Straus (94) discussed above could possibly also have such a sig- 

 nificance, since the kidneys of animals treated with egg-white certainly show 

 some degenerative changes, for instance of mitochondria (70). But the high free 

 activities of lysosomal enzymes found in the homogenates of these kidneys could 

 also reflect the enhancement of their pinocytic activity. A similar explanation could 

 account for the high free activities of normal spleen homogenates and also for the 

 relatively low content in lysosome-like particles of Kupffer cells (102). The dis- 

 tinction between pathological and physiological free enzymes would then depend 

 on whether they are truly free in the cytoplasm or segregated within fragile 

 digestive vacuoles. 



Physiological Autolysis. Autolysis occurs as a physiological process in the life 

 history of some organs (involution of the thymus at puberty, of the uterus after 

 parturition, etc.); it plays a major role in the metamorphosis of insects and oi 

 some other zoological groups; it may also intervene in some secretory processes, 

 in particular in those of the holocrine type. The possible involvement of lysosomes 

 in any of these phenomena has so far not been studied, with the exception of a 

 recent investigation by Weber (104, 105) bearing on the catheptic activity of the 

 tail of Xenopus larvae. Weber finds that the specific activity of this enzyme de- 

 creases during the growth phase of the tail and increases during its subsequent 

 resorption, reaching up to 22 times its initial level in the final stages of meta- 

 morphosis. He concludes that this enzyme plays no part in protein synthesis but 

 is involved in proteolysis. Whether cathepsin is particle-bound in the investigated 

 tissue is, however, not known. 



In addition to these specialized processes, some degree of autolysis must be 

 taking place in many if not all tissues, as is evidenced by the observed turnovers 

 of their main constituents. So far, a great deal of work has been performed on 



