DEVELOPMENT AND FUNCTION OF MACROPHAGES IN BONE-REPAIR. 13 



in the diluted extensions of the Haversian canals, a cell well studded with dye- 

 granules is often encountered. In size and general appearance these are quite 

 similar to the macrophages which inhabit the actively growing regions of develop- 

 ing bone described by Shipley and Macklin (1916 2 ), as shown by a comparison with 

 the specimens of these authors, and also with sections from the end of a growing bone 

 from the same animal (S 11-1) from which the fracture-sections were cut. In the 

 Haversian canals of the adjacent normal bone, cells containing dye-granules are 

 rare; when they do occur they are of small size and slight degree of staining. In 

 no case are the trypanophil cells of the callus at this stage at all comparable in size 

 and staining intensity with the extraosseous phagocytes of the degenerating tissues; 

 indeed, when compared with these they are quite insignificant. 



As to the function of these trypanophil cells, it is noteworthy that some slight 

 breaking down of tissue occurs in association with the hollowing-out of the inter- 

 trabecular spaces, and it may well be that they are being developed to absorb the 

 waste products resulting from this process. In any event their advent in the spaces 

 is coincident with the enlargement of the latter. Of even greater significance, 

 however, is their importance in these early stages as examples of phagocytic pre- 

 paredness, for, as will be later seen, it is these cells which light up suddenly into 

 vigorous action coincidently with the onset of very active bone resorption, which 

 begins about the tenth day. 



The source of the trypanophilic cells in the spaces of the callus would seem to 

 be the tissue of the Haversian canals of the old bone. They are doubtless of the 

 same type as the reticulo-endothelial macrophages found in ordinary bone marrow. 

 Under the conditions of bone erosion they have increased in size and phagocytic 

 ability, for their well-developed representatives are obviously much larger and 

 more deeply stained than the cells of the non-growing bone marrow. 



In the third-day stage, then, it is evident, judging from the structure of the 

 bone, that osseous resorption is under way to a limited extent in the Haversian 

 spaces immediately underlying the new callus and in the spaces of the callus itself. 

 It is significant that trypanophilic cells should make their appearance in the spaces 

 which are being hollowed out simultaneously with the onset of this process and 

 that there should be a direct relationship between their size and staining intensity, 

 on the one hand, and the extent of the bone-excavation on the other. 



The callus of the skull, though not so far advanced as that of the long bones, 

 is of the same general character. 



Summarizing the features of the staining at the third day, we may first mention 

 the immense congregation of macrophages which are evidently engaged in clearing 

 away the debris consisting of blood-clot, damaged muscle, bone, and other tissues. 

 The great majority of these are apparently developed from the lymphocyte-like 

 cells, brought by the blood-stream to the site of the fracture, where they rapidly 

 gain in size and phagocytic power. Their function is the phagocytosis of waste 

 products from tissue breakdown. Diffuse staining of the defunct tissue is present. 

 In the expanding spaces of the growing callus trypanophilic reticulum cells have 



