X ROLE OF S IN WOUND HEALING 7OI 



(Williamson et al., 1951a; Williamson and Fromm, 1952, 1953b; Williamson et 

 al., 1951a). The -^^S content of skin is doubled five days following woimding 

 (Williamson and Fromm, 1953b) and there is a decrease in wound tensile strength 

 when iodacetic acid, which blocks sulfhydryl groups, is given parenterally (Chassin 

 and Localio, 1949). The amino acids methionine and cystine have the same effect 

 on healing as protein (Williamson et al., 1951a, b; W'illiamson and Fromm, 1952, 

 1953a, 1954b; Cuthbertson, 1946; Localio et al., 1948; Peters, 1945; Croft and 

 Peters, 1945). Normally, there is more methionine in tissue than cystine; how- 

 ever, in healing wounds the rate of cystine deposition is greater and appears 

 directly related to the healing index (Williamson and Fromm, 1953b). When 

 radioactive -^^S labeled L-methionine is injected into protein-depleted animals the 

 majority appears in granulation tissue as cystine ^^S. This conversion of methionine 

 to cystine is irreversible (Binkley, 1944; Du Vigneaud et at., 1944), therefore, 

 cystine is the limiting amino-acid in healing. Animals given ^^S DL-cystine excrete 

 more sulfate sulfur, the end product of sulfur metabolism, than animals receiving 

 -^^S DL-methionine. This is to be expected as methionine can be used per se or for 

 conversion to cystine, whereas the latter is only available for incorporation into 

 protein. Liver methionine normally acts as the source for cystine is this process 

 (W'illiamson and Fromm, 1955). 



The tensile strength of wovuids is correlated with the amount of cystine or 

 methionine as well as the collagen content. These amino acids are almost entirely 

 bound to the proteins of wound tissue ; however, collagen, the principle protein, 

 contains neither of these. This would indicate that collagen formation is related to 

 these amino acids in a manner as yet unknown. There is a delayed production of 

 both mucopolysaccharides and collagen in the wounds of protein depleted animals 

 (Udupa et al., 1956), these substances are restored to normal upon addition of 

 methionine to the diet. Although the action of methionine or cystine upon 

 granulation tissue is obscure it has been postulated that these amino acids 

 may increase the efficiency of protein metabolism (Forbes, 1954), by stimu- 

 lating the growth of fibroblasts (Morgan and Morton, 1955) or in the case of 

 polysaccharides by donating sulfate ions. Williamson's work (Williamson and 

 Fromm, 1955) demonstrates that at least two different types of protein are pro- 

 duced in granulation tissue. During the early stage the protein contains a larger 

 ratio of methionine than cystine, whereas later the cystine predominates. The 

 scope of protein metabolism in healing has been recently presented by Williamson 

 {1956) and will not be reviewed here. 



XI. SUMMARY 



Wound healing is a complex process and many basic problems still remain un- 

 solved. The over-all pattern consists of initial cell migration followed by an in- 

 crease in cell numbers, however, the manner and rate varies considerably for the 

 component tissues. The stimulus which initiates this chain of events is the inter- 

 ruption in cell continuity but the mechanism of this process is entirely unknown. 

 No chemical substance which would fit the definition of a wound hormone has so 



Lileralure p. 703 



