38 DEVELOPMENT AND FUNCTION OF MACROPHAGES IN BONE-REPAIR. 



the tissue here is eroded this active zone shifts outward and at the fifteenth day it 

 occupies the interior of the mass. From here the zone advances, in turn, to the 

 periphery, and the redundant material is cleared away in that region. Certain 

 areas of bone, necessary for the stability of the callus, are conserved, and these 

 are thoroughly reinforced through the application of layer upon layer of bone by 

 the activities of the osteoblasts. 



During this period the intraosseous phagocytes, as demonstrated by vital- 

 staining, are exceedingly striking. In regions where obviously bone erosion is 

 proceeding most vigorously they now devour the dyestuff much more greedily and 

 store it in the form of larger and more numerous granules. In their more intense 

 staining they form a striking contrast to the cells of the developmental phase. 

 Thus, in the earlier stages of this period, at the tenth and twelfth days, the largest 

 macrophages are found crowded in the spaces near the original bone; on the fifteenth 

 day they have shifted to the interior of the callus, and on the twentieth day (keeping 

 pace with the outward movement of the zone of most active bone destruction) 

 they have again shifted their ranks to the peripheral regions of the callus, the more 

 central areas containing relatively few of them. 



This localization of the demolition-zones is not absolute, for (especially in 

 the later stages) detachments of hypertrophied macrophages may be found in nooks 

 and corners throughout the callus wherever bone is being actively resorbed. Again, 

 in some of the ribs (perhaps because there was less movement of the fragments) 

 the callus was less and its removal was accomplished apparently by a process of 

 paring down from the periphery, the bone becoming more and more slender, as the 

 figures of cleared ribs indicate. It is quite obvious that concentration and hyper- 

 trophy of macrophagic tissue are inseparably linked with active bone erosion. 



As time goes on, the macrophages of the reticulum undergo, in the areas of 

 active bone destruction, a certain amount of progressive enlargement, the largest 

 cells having an average long diameter of 7.6 n, 9.15 n, 9.95 n, and 12.6 /j. on the 

 tenth, twelfth, fifteenth, and twentieth day respectively. With this hypertrophy 

 there is some increase in the amount of the dyestuff stored, indicating an exalta- 

 tion of phagocytic power. Mitotic figures in reticulum cells, many of which 

 contained dye, were found throughout this period of activity. A few smaller and 

 less brilliantly stained reticulum cells are found in all parts of the callus tissue. 



The manner of action of the reticulum macrophages presents some features 

 of interest. There is nothing to support the idea that they carry on, contribute to, 

 or even initiate the actual process of callus destruction. Their position in the 

 reticulum never in actual contact with the bony structure does not, to say the 

 least, lend support to any such hypothesis; nor is there any evidence pointing to 

 the elaboration, by these cells, of a secretion such as an acid or a proteolytic 

 enzyme which would act in the liquefaction of the callus. On the other hand, 

 there is positive evidence of the most convincing kind the avidity with which 

 these cells ingest colloidal dyestuff s that they play the role of phagocytes; like 

 the polyblasts of degenerating soft tissues, or the reticulo-endothelial cells of 

 developing bone, they ingest the products of tissue breakdown. 



