MYELOID METAPLASIA OF THE EMBRYONIC MESENCHYME. 29 



splenic tissue. The presence of such tissue in the economy of the embryo is fol- 

 lowed by a myeloid metaplasia of the mesenchyme in the host. Moreover, the un- 

 differentiated mesenchyme of the adult splenic tissue in the graft itself undergoes 

 such differentiation. There must be a common cause for both of these phenomena. 

 Some valuable information concerning these factors may be gained by com- 

 parison of the present results with other well-known cases of excessive production 

 of granular leucocytes. Though these instances concern mammals, the cause in 

 both can not differ much, since the whole process of granuloblastic differentiation 

 is found to be the same for both classes of animals. The granulopoietic activity of 

 the bone-marrow is greatly increased in an adult organism by acute inflammatory 

 processes. A granuloblastic differentiation (the myeloid metaplasia) can be incited 

 in lymphatic organs by various agents. Discussing in one of my previous publica- 

 tions (1916<?) this effect upon the mesenchyme of the host's spleen, I stated: 



"It is important to notice that the myeloid metaplasia is produced by different causes. 

 The toxins of various bacteria, the specific products of metabolism of malignant tumors, 

 finally, inorganic chronic intoxications, may incite an extensive myeloid metaplasia. It is 

 difficult to conceive, in such qualitatively different agents, a specific stimulating influence on 

 the stem cells. The response to the action of these factors is specific in so far as it is exhib- 

 ited by a certain kind of tissue (even not of cells). The stimulus itself may largely vary." 



At that time the process of myeloid metaplasia presented itself to my mind as 

 a result of the direct action of the factors introduced upon the mesenchyme, and 

 therefore each of them must, in my opinion, have found in the same cells different 

 receptors in order to be capable of bringing them to a proliferation. I do not know 

 how otherwise we could explain an identical result obtained by such different factors 

 as acute inflammation, inorganic intoxications, or malignant tumors; that is to say, 

 if the myeloid metaplasia is conceived as resulting from a direct action of the 

 agents cited upon the mesenchyme. But the myeloid metaplasia may be the 

 result of a reaction of the mesenchyme to some secondary changes produced in 

 the organism by the different factors and similar in all cases. It is possible, indeed, 

 to find in the seemingly so different etiology of the myeloid metaplasia features com- 

 mon to all the cases. My present task will be only to point them out as factors which 

 may be in some way connected with the developing activity in the mesenchyme. 



In acute infections, besides the appearance in the organism of various new 

 substances secreted by the bacteria, a more or less extensive injury of normal tissue 

 takes place. Different kinds of cells die and remain in the organism in the form of 

 small particles of unaltered protein. Though new to the organism, this situation 

 is readily met with. The phagocytic and high digestive power of the endothelial 

 cells of the cellular reticulum in the lymphatic organs and that of the mature 

 fibroblasts (in the case of nerve degeneration, for example) toward various protein 

 inclusions is well known and is usually sufficient in order to localize and to overcome 

 a banal infection. Small protein particles in the form of dead cells are directly 

 ingested by the mesenchymal cells and undergo an apparently complete intracellular 

 digestion . A local infection of short duration will not produce a myeloid metaplasia of 

 the undifferentiated mesenchyme in all the hemopoietic organs, but will only increase 



