DEVELOPMENT AND FUNCTION OF MACROPHAGES IN BONE-REPAIR. 39 



The particular tissue-destruction with which the reticulum macrophages have 

 to do is that of callus. In this destructive process we recognize two aspects: (1) the 

 removal of the bone-salts; (2) the removal of the matrix with its contained cells. 



It is becoming more and more clear that the process of removal of the bone- 

 salts from the matrix is simply the reverse of that of their deposition in ossification ; 

 that we have here to do with the reverse phase of a chemico-physical reaction whose 

 direction is determined solely by the conditions of the immediate environment. 

 Under certain circumstances, apparently centering around definite and well-ordered 

 changes in the local blood-vascular system, there are precipitated from the circu- 

 lating fluids into a special matrix (elaborated by the activities of definite specialized 

 cells, the osteoblasts) certain insoluble building-materials, the bone-salts. These 

 consist mainly of calcium phosphate and calcium carbonate, their quantitative 

 relations being determined by their relative solubilities in the blood-plasma. There 

 is here simply a cell-controlled calcification (Wells, 1911; Macklin, 1917). 



In deossification, or more accurately decalcification, the reverse process is 

 encountered. Changes, particularly in the circulating fluids, cause the bone-salts 

 to be released from the matrix and again taken up into the blood; the matrix and 

 bone-cells remain; the former is liquefied, by means at present obscure. As to the 

 latter, there is ground for the view that they are sometimes left in heaps like drift- 

 wood; that they even coalesce to form giant-cells (Arey, 1917). It is probable that 

 many are disintegrated, to swell the volume of the liquefied waste-products. 



That the liquefied bone-salts are phagocytized by the macrophages seems 

 doubtful. They are non-toxic and probably pass off into the circulating blood in a 

 manner the reverse of their incoming. It does seem probable, however, that the 

 phagocytes ingest some, at least, of the products resulting from liquefaction of the 

 protein-content of the callus. Their function would thus be closely allied with that 

 assumed for the wandering macrophages of the degenerating extraosseous tissue. 

 Here, too, it may be postulated that their service is protective; that they guard the 

 organism from the harmful effects of toxic, nitrogen-containing compounds resulting 

 from proteolysis. It is quite possible that only certain of the compounds arising 

 from tissue breakdown are poisonous, and that only these are ingested. As in the 

 case of the polyblasts, it may be assumed that the materials so phagocytized are 

 digested and rendered innocuous or even useful within the cytoplasmic laboratory 

 of the macrophages. 



It has been noted that the treatment by the macrophages of high-molecular 

 dyestuffs, such as trypan-blue, is an expression of their general behavior toward 

 any material in the same physical condition; and it has been inferred, therefore, by 

 Shipley and Macklin (1916 2 ), that the material resulting from the erosion of pro- 

 visional cartilage and bone, which is phagocytized by the macrophages, is in a 

 finely dispersed state. Such an inference may also be made for the waste products 

 resulting from the erosion of callus or from the breakdown of the soft tissues 

 around the wounded bone. 



The position of the macrophages of the demolition zones in the loose reticulum 

 of the spaces is favorable to the exercise of their function, for they, like the poly- 



