DEVELOPMENT AND FUNCTION OF MACROPHAGES IN BONE-REPAIR. 41 



the older stages the cartilage underwent changes similar to those of ossification of 

 cartilage in normal skeletal development. A case was found where the cartilage 

 had even taken all the characters of a typical epiphysial plate. Associated with the 

 process of destruction of the cartilage, and of the trabecula? of bone built upon the 

 calcined remnants, macrophages played the same part as in the normal endo- 

 chondral ossification, as shown by Shipley and Macklin (1916 2 ). 



Giant-cells or "osteoclasts" were found not infrequently in the callus of some 

 of the specimens, and rarely in others. Their numbers seemed to have no relation 

 to the amount of bone destruction; thus none was observed on the tenth day, a 

 few on the twelfth, they were fairly numerous on the fifteenth, but scarce on the 

 twentieth day. In all of these stages there was undoubtedly a great deal of bone 

 erosion progressing. Again, at the same stage but in different specimens, they were 

 inconstant in number ; thus in one of the specimens of the six-day stage there were 

 very few, while in the other specimen a fair number was found. In no case was 

 there a large enough number, nor were the cells sufficiently well distributed, to 

 warrant regarding them as the agents of bone erosion. Careful search was made 

 for dye-granules in them, but not a trace was to be found; hence they are not phago- 

 cytes of the type of the macro phages. Indeed, no ingested material of any kind 

 could be found in them. Thus the giant-cells of the callus and the underlying old 

 bone in process of erosion are in these respects quite the same as the giant-cells of 

 developing bone described by Shipley and Macklin (1916' 2 ). 



COMPARISON OF EXTRAOSSEOUS AND INTRAOSSEOUS MACROPHAGES. 



It is of interest to compare briefly the macrophagic cells of the callus with those 

 of degenerating extraosseous tissue. They have many points of difference. The 

 callus cells are fixed and belong to the reticulum tissue, whereas the cells of the soft 

 parts are mostly wandering and are derived from the "resting- wandering cells" of 

 the tissues and from certain lymphocyte-like cells brought in the blood-stream. 

 It is probable, however, that cells originating from the reticulum and endothelium 

 of the bone-marrow of the broken bone-edges contribute to the forces of the extra- 

 osseous macrophages in their vicinity. The callus cells develop in situ, whereas 

 the cells of the soft parts begin their development probably for the most part out- 

 side the zone of their operations; however, both no doubt undergo their hypertrophy 

 mainly at the site of tissue-breakdown. The callus-cells multiply in situ by mitosis 

 (typical figures being found in dye-containing cells as early as the sixth day and as 

 late as the twentieth) , whereas most of the cells of the soft parts undergo multipli- 

 cation at their source. The largest of the extraosseous macrophages are of greater 

 size than the phagocytes of the callus, and usually contain more dyestuff, their 

 granules, as a rule, exceeding in magnitude those of the callus-cells. 



It seems probable that the demands upon the macrophages of the soft parts 

 are much heavier than those which the callus-phagocytes are called upon to meet, 

 the waste material being much greater in the damaged soft parts than in the resolv- 

 ing callus. Hence the cells of the callus never reach the physical proportions nor 

 the great numbers of the cells of the soft parts. The effort of the extraosseous cells 



