IX ALKALINE PHOSPHATASE 699 



The alkaline phosphatase was located in the cytoplasm of fibroblasts as well as 

 in association with newly formed fibrils which has been verified by Firket (1951) 

 and Washburn (1955). According to Danielli et ai, (1945) a direct relationship 

 exists between phosphatase activity and the degree of collagen formation in 

 scorbutic animals; however, Bunting and White (1950) were unable to substantiate 

 this in partially scorbutic guinea pigs. Normally, mammalian dermis contains 

 only small amounts of alkaline phosphatase limited to the outer sheath of hair 

 follicles, sebaceous gland, and perivascular fibrocytes (Fisher and Glick, 1947). 

 Phosphatase has been demonstrated in some areas of fibrous protein synthesis 

 (Johnson et al., 1945; Johnson and Bevelander, 1946) but not in others (Marchant, 

 1949; Robertson et al., 1950). In view of the fact that freshly precipitated collagen 

 fibers firmly bind alkaline phosphatase in vitro (Gold and Gould, 1951) it is 

 questionable that this enzyme plays any role in collagen formation. Furthermore, 

 in wounds the local concentration of phosphatase is independent of the serum 

 level and there is no evidence that phosphatase inhibitors impair wound healing 

 (Gould and Gold, 195 1). There is considerable parallelism between the activity 

 of alkaline phosphatase in mammalian wounds and the normal ontogeny of 

 organisms. The enzyme appears to be most concentrated in areas of cell differen- 

 tiation. Little is found in the early embryo (Brachet, 1946; Moog, 1944) or in 

 well diflferentiated tissues except where it is related to specialized functions. 

 During diflferentiation of amphibian limb buds or in regeneration of new limbs 

 there is a marked increase in the mesenchymal cells. Karczmar and Berg (1951) 

 suggested that differentiating cells may pass through a transition phase rich in 

 alkaline phosphatase. There appears to be, however, a direct relationship between 

 epithelium and phosphatase. W'hen epithelium is buried in the subcutaneous 

 or muscle tissue of an animal a pronounced alkaline phosphatase reaction is 

 detected about the newly formed connective tissue; control areas reveal no such 

 reaction (French and Bendit, 1954). Gomori (1943) has suggested the possibility 

 that bladder epithelium, which evokes the same reaction when transplanted, may 

 have a specific inductive power leading to the growth of phosphatase-producing 

 fibrocytes. Normally, cultures of fibroblasts contain no alkaline phosphatase 

 (Willmer, 1942; Rodova, 1948; Chevremont and Firket, 1949); however, in old 

 cultures when cells begin to degenerate the cytoplasm is rich in this enzyme 

 (Henrichsen, 1956). It is of interest to note that alkaHne phosphatase has also been 

 detected in the granules of mast cells (Noback and Montagna, 1947). The reaction 

 is limited to the mouse and rat and occurs most commonly in those situated 

 perivascularly (Riley and Drennan, 1949). These authors beheve that phosphatase 

 is somehow concerned with elaboration of the metachromatic substance. 



X. ROLE OF SULFUR IN WOUND HEALING 



Studies using radioactive sulfur ^^S hav^e proved useful in gaining further infor- 

 mation about the composition of the dermis under physiological conditions and 

 during wound healing. If a tracer dose of ^^S is given to an animal, the majority 

 (95%) is rapidly eliminated (five days) although a small portion remains in the 



Literature p. yo3 



