688 WOUND HEALING 8 



where there is an increased mitotic rate would therefore contain greater amounts 

 of the enzyme. No explanation for the corresponding decrease in non-specific 

 esterase content has been proposed. 



VI. SOURCE OF GRANULATION TISSUE 



The wounding of a skin surface induces a response not only from adjacent epi- 

 thelium but also from the underlying dermis. Indeed the degree to which epi- 

 thelialization is successful in covering a wound is largely dependent upon this 

 dermal response. Although the histological sequence during formation of granula- 

 tion tissue is well known, the origin of the cellular eleinents is still debated. Three 

 theories exist : (i) the granulation tissue is formed from foreign cells brought to the 

 local site by the blood stream, (2) the cellular elements are formed entirely from 

 local tissue adjacent to the wound area, {3) both local and distant elements are 

 involved. 



{a) The evidence in favor of blood stream elements forming the cellular con- 

 stituents of granulation tissue has been presented by Allgower (1956). A brief 

 summary of his review will suffice. Maximow in 1902 stated that any theory based 

 upon local origin of granulation tissue fails to account for the rapid accumulation 

 of new cells which takes place in the absence of an increased mitotic rate. In young 

 wounds, an ameboid round cell with a large eccentric nucleus (polyblast), could be 

 observed and he believed that polyblasts, lymphocytes, and clasmatocytes were 

 actually transitional forms of this cell, the clasmatocyte ultimately being indistin- 

 guishable from a fibroblast in the healed wound. Evidence to support the contention 

 that lymphocytes can be transformed to fibrocytes is lacking. Indeed, HuUiger 

 ( 1956) found that cultures of "lymph buffy coat" failed to form a tissue network as 

 did blood cultures (Allgower, 1947). 



Although lymphocytes probably play no role in granulation tissue formation, 

 such a role may be assumed by other white cell elements (Danchakoff, 191 6). 

 This theory has also been contested by Clark (1956) and others (Herzog, 1923; 

 Freund, 1931 ; Stearns, 1940a), who have concluded that blood elements play no 

 part in the formation of connective tissue. Ebert, Florey and Pullinger (1939), 

 however, observed that India ink particles when injected into a wounded animal 

 could be found in histocyte-like cells of the wound and they believed that the blood 

 monocytes were most probably converted to histocytes in the granulating area 

 (Ebert and Florey, 1939). 



Allgower (1956), using the rabbit ear as a test object, reported a 50% to 70% 

 reduction in the quantity of granulation tissue in animals that received sufficient 

 total body irradiation to lower their leukocyte count from 7,000-10,000 to 300-600 

 per mm3. Interestingly enough, this occurred in shielded ear wovmds as well as in 

 those exposed to x-ray, which is strong evidence for the hypothesis that leukocytes 

 play a role in the granulating reaction. Needless to say, the effects of total body 

 irradiation are profound. The possibility that some equally important factor (or 

 factors) could also be influenced by irradiation has not been disproved. 



In tissue culture the leukocytes assume a spindle shape and strongly resemble 



