DEVELOPMENT AND FUNCTION OF MACROPHAGES IN BONE-REPAIR. 29 



EXTRAOSSEOUS MACROPHAGES. 



A survey of the specimens from the experimental animals has shown that the 

 maerophage tissue of the soft parts at the wound-site, after a brisk initial rise fol- 

 lowing the injury, remains at maximum for a few days and then gradually falls 

 away. During the first two or three days these phagocytes may be considered as 

 undergoing mobilization and development. Noticeably increased at the end of 

 48 hours, they are on the third day very abundant, and so continue during the 

 fourth, fifth, and sixth days, after which their numbers gradually diminish. In 

 the long bones they are not very marked after the fifteenth day, and in the ribs and 

 skulls, since their work is less, they do not persist so long, being reduced almost to 

 normal by the tenth day, or shortly after. This rise and fall is graphically shown 

 in the series of cleared specimens, especially in the ribs, where the area surrounding 

 the wounded bone speedily becomes blue from the accumulated vitally stained 

 cells and (after remaining so for a few days) gradually pales. Sections from the 

 skull and long bones serve to support this finding. 



In studying this increased macrophagic tissue from day to day, one is impressed 

 by the close association wluch it has with the waste material, the result of the 

 trauma. Again and again has it been noted that, where tissue-waste is present in 

 large amount the macrophages are enormously increased, and that as the debris 

 disappears the macrophagic tissue gradually becomes less marked. Indeed, so 

 close is this relationship that the curve tracing out the chronological record of 

 macrophagic intensity roughly parallels that described by the slowly disappearing 

 waste tissue. These facts will be apparent from the following review. 



The evidence presented by the cleared ribs shows that damaged tissue and 

 exudate, as manifested by diffuse staining of material in the region of the fracture, 

 was, on the second and third days, strongly marked; on the fifth day somewhat less 

 conspicuous; on the sixth day still more reduced; and after this it was not observed. 



In comparison, it is to be noted that the macrophages at the fracture-site were 

 somewhat increased over the normal on the second day, and on the third day were 

 very markedly increased, remaining so until the fifth and sixth days, and being 

 reduced on the ninth day. They then gradually diminished. This relation of the 

 macrophages to the demonstrable debris at the fracture-site is graphically set out 

 in table 2, which shows a synchronism, as evidenced by the cleared specimens and 

 sections, between the occurrence of debris (representing dead and dying tissue) and 

 that of macrophages in increased numbers in the vicinity of the debris. Some 

 variations in individual specimens are noted. Thus in the fifteenth and twentieth 

 day stages of the long bones the macrophages are unusually numerous, probably 

 due to the severity of the injury. Again, the skull sections show more debris and 

 as many macrophages on the tenth day as on the sixth; this is due to an infection 

 in this case. 



In the cleared skulls, as shown in table 2, the findings are very similar. Debris 

 was strongly marked on the second, third, and sixth days, becoming less on the 

 ninth and not appearing after the tenth day. Its removal was thus accomplished in 



