DEVELOPMENT AND FUNCTION OF MACROPHAGES IN BONE-REPAIR. 21 



found in which areas of cytoplasm are without visible dyestuff. In the typical 

 phagocytes of this stage the granules are much larger than in I lie earlier st:iges, 

 and there are more of them. There is much more dyestuff in the cell. 



Some of the cells contain a very few quite large granules of dyestuff instead of 

 a multitude of smaller ones, suggesting that there has been a coalescence of the 

 latter. Again, in an occasional cell, the appearance is as though the entire nucleus 

 were stained, pointing to the death of the cell. It is possible that these cells have 

 succumbed to the action of the material ingested; or such appearances may be due 

 to stained protoplasmic inclusions. Similar findings have been noted in extraosseous 

 macrophages. 



As the cell fills with its pabulum or with dye it becomes more rounded and 

 the processes are reduced to fine threads. As a rule, the dyestuff does not find its 

 way far into the processes, so that the dye-granule contour is usually oval, as is 

 seen in figure 15, drawn from representative uncounterstained reticulum macro- 

 phages of different periods. 



A few polymorphonuclear leucocytes are seen associated with the macrophages. 

 No dyestuff was found in them. Osteoblasts are sometimes met with in their 

 vicinity, but never take the dyestuff. Giant-cells were not encountered. 



In the skitll of this stage (S 5-1) distinctly stained reticulum cells were found 

 in the spaces in the callus and also in the old bone. 



As will be seen from the examination of the subsequent stages, the resorption 

 of the callus is most active during the period from the tenth to the twentieth day 

 or shortly after; before that period the main trend in the callus is constructive 

 rather than destructive, although, as has been pointed out, there is, even during 

 this evolutionary phase, some hollowing-out of the spaces, as seen, for instance, in 

 the specimens of the fifth and sixth days. Furthermore, the stages from the tenth 

 to the twentieth day show that the greatest amount of resorption occurs at first in 

 the vicinity of the old bone, for the spaces there undergo the greatest expansion. 

 It is thus evident that the most brilliantly stained, and hence the most phagocytic, 

 cells are found where callus destruction is most active. It is plain, too, that these 

 cells have undergone an exaltation of their powers of phagocytosis coincidently 

 with the acceleration of callus resorption. 



Reviewing the tenth day it is noted that extraosseous macrophages are grad- 

 ually disappearing, as shown by the many degenerate forms and by the relative 

 inconspicuousness of the survivors. Their place is taken by scar tissue. In the 

 callus the most striking point is the marked hypertrophy and increase in phago- 

 cytic ability of the macrophages of the reticulum of the callus spaces undergoing 

 expansion at the expense of their osseous walls. 



TWELFTH-DAY STAGE. (S 5-2). 



Little or no stained debris was noted in the cleared skull of the twelfth day, 

 nor was it found after this stage. In this specimen the opening in the bone was 

 left unfilled. The central part of this opening is almost clear, being occupied by 



