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Accruing evidence indicates that the levels of extracellular Mg2+ and Ca2+ can have a distinct impact on the adhesive and migratory activities of many cell types. The physiological relevance of these observations, however, has remained largely unexplored. In the present study, wound fluids collected throughout the early stages of cutaneous wound repair were examined for possible Mg2+ and Ca2+ fluctuations. Early in the process, when cell migration into the wound site is initiated, Mg2+ is elevated and Ca2+ is reduced (Mg2+:Ca2+ = 1). As wound healing progresses, wound fluid concentrations of Mg2+ and Ca2+ begin to return to normal plasma levels (Mg2+:Ca2+ = 0.4). When macrophages, keratinocytes, fibroblasts, and endothelial cells were exposed to dialyzed wound fluid, the migration stimulated by undialyzed wound fluid was lost. Addition back to dialyzed wound fluid of 24 h, postinjury concentrations of Mg2+ and Ca2+ restored all migratory stimulus. This observed migration is approximately twofold greater than when normal plasma Mg2+ and Ca2+ concentrations are present. Changes in the levels of Mg2+ and Ca2+ in wound fluid occur during the same period that inflammatory cells, keratinocytes, fibroblasts, and neovasculature have been shown to migrate during wound healing in vivo. Together, these data suggest that the impact of these changes on integrins and E-cadherin may play a direct role in the activation and maintenance of the migratory phenotypes of the cells involved in the wound healing process.

Shifts in the concentrations of magnesium and calcium in early porcine and rat wound fluids activate the cell migratory response.