Metalloenzymes have an important role in repair and regenerative processes in skin wounds. Demands for different enzymes vary according to the phase in the healing cascade and constituent events. Sequential changes in the concentrations of calcium, copper, magnesium and zinc were studied in the incisional wound model in the rat over a 10 d period. Copper levels remained low ( 10 µg\g dry weight) throughout, but calcium, magnesium and zinc increased from wounding and peaked at about 5 d at a time of high inflammation, granulation tissue formation and epidermal cell proliferation. Metal concentrations declined to normal by 7 d when inflammation had regressed, re-epithelialisation of the wound site was complete and the ' normalisation ' phase had commenced. Although the wound was overtly healed by 10 d, the epidermis was still moderately hyperplastic. In view of competitive binding of trace metals at membrane receptors and carrier proteins, the ratios or balance between these trace metals was examined and the significance is discussed. Using immunocytochemistry, we demonstrated increases in metallothionein immunoreactivity as an indication of zinc and copper activity in the papillary dermis and in basal epidermal cells near the wound margin 1-5 d after wounding. This is consistent with metalloenzyme requirements in inflammation and fibrogenesis. Calmodulin, a major cytosolic calcium binding protein was highest in maturing keratinocytes and in sebaceous gland cells of normal skin ; it was notably more abundant in the epidermis near the wound margin and in re-epithelialising areas at a time when local calcium levels were highest.Key words : Skin wounds ; repair ; trace metalloenzymes ; metal ion balance ; zinc ; calcium ; copper ; magnesium.
Wound healing in the skin and in other tissues of the human body depends upon the availability of competent cells to carry out repair processes, appropriate activation by hormones, growth factors, cytokines and chemotactic factors, and a microenvironment favouring cell movement, proliferation and functional maturation (Grotendorst, 1992 ;Hunt & Hussain, 1992). Metal ions and metalloenzymes feature prominently in this wound healing environment and experimental and clinical studies are available to show that deficiencies in zinc, copper, calcium, iron or magnesium are potential causes of abnormal homeostatic mechanisms and impaired wound healing (Moynahan, 1974 ;Lansdown, 1995) tention recently has focused upon the role of metalloproteinases in the degradation of extracellular matrix in the early phases of wound healing (Nwomeh et al. 1998), it is to be expected that the demands for these and other metalloenzymes will vary greatly as the profile of wound healing proceeds. Surprisingly, the action and interaction of trace metals in the skin under normal conditions is not well documented, and sequential changes in the healing wound are not published for any species (Lansdown, 1995).Much of the trace metal requirement for the body is derived from the diet, but many...