DEVELOPMENT AND FUNCTION OF MACROPHAGES IN BONE-KEPAIR. 25 



In the cleared skull of the twentieth day the extraosseous macrophages show 

 little if any increase above normal. The membrane of connective-tissue filling in 

 the intervals between the bone pieces stains diffusely blue, especially where it is 

 thickened near the edges, but this staining is not strongly marked and resembles 

 the staining of any similar fibrous connective-tissue, as tendon (foot-note, page 8, c). 

 A few persisting macrophages appear in it. The new bony callus is abundant 

 and in its spaces a few trypanophilic cells are seen. 



In the sections of the loiuj hones of the twentieth day (S 12-2, S 13-2) large areas 

 of callus and of scar-tissue are conspicuous. Near the fracture the muscle-fibers, 

 as noted for the two last-mentioned stages, are often scattered and surrounded by 

 the new scar. They are frequently rounded and dwarfed. Numbers of macro- 

 phages still persist in places such as this; probably they are not actively functioning 

 and gradually disappear, for, barring a few found at the thirtieth day, they are not 

 encountered in future stages. No evidence of extraosseous proteolysis is to be seen, 

 there being no blue-staining debris or degenerate tissue. Transitional cells were 

 not found in the twentieth-day stage. 



The callus of the long bones (S 12-2) of the twentieth day is especially inter- 

 esting. At no stage are there greater evidences of erosion. Enormous spaces 

 characterize the cross-sections and in some of these but a mere shell of bone remains 

 at the periphery, while the central region is filled with marrow-tissue, tunneled 

 by large blood-sinuses. Again, in other sections the spaces are partitioned by 

 stout trabecula? of bone. A corner of a typical section is presented in figure 17. 

 Here the most spectacular feature, brought out with singular sharpness in the 

 cleared section, is the multitude of brilliantly stained reticulum macrophages at 

 work in the smaller spaces. As a rule they are now massed in the more peripheral 

 recesses, though some crowd into corners here and there throughout the bony 

 spongework, where temporary osseous scaffolding still awaits removal. A few 

 haunt the interstices of the marrow tissue. In many areas they are very incon- 

 spicuous or absent. Here bone erosion has evidently ceased. It is obvious that the 

 area of most active bone destruction has shifted from the central mass of the callus 

 to the more outlying regions and, as in the last stage, the macrophagic army has 

 kept pace with this onward march. 



Striking indeed are the pictures presented under the higher powers. In figure 

 18 is seen a small field, magnified 190 times, from the section from which figure 17 

 was taken. The formations of macrophages (M), as before, are drawn up in the 

 perivascular spaces or deployed through the loose reticulum. In these areas of 

 most active bone-erosion the phagocytes are even larger in size than at the fifteenth 

 day, for the average measurement of the longest diameters of ten of the largest 

 cells was 12.6 microns, in contrast with 9.95 microns, the average at the fifteenth- 

 day stage. These compare in size with the large extraosseous macrophages. Typi- 

 cal uncounterstained cells are shown in figure 15, d. Mitoses in dye-containing cells 

 are present, but are not frequently found. 



