This review focusses on two questions: (1) How can the intracellular toxicity of ions such as Ca2+ or Zn2+ be reconciled with their extracellular benefit? (2) Why is the dietary requirement for Zn2+ so high when its documented biological role is that of a tightly-bound prosthetic group of certain enzymes? An answer to both questions is provided by the observation that extracellular cations such as Ca2+ and Zn2+ protect the plasma membrane of cells against non-specific leakage, including an influx of Ca2+ or Zn2+. It is suggested that such protection, against leakage induced by microbial and other toxins, may contribute to the high dietary requirement for zinc. These arguments lead to the proposal that a previously unrecognized form of host defence is one of protection of the cell plasma membrane by divalent cations against damage induced by cytotoxic agents of environmental origin.

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