Wound-induced calcium waves in alveolar type II cells

Alveolar type II epithelial (ATII) cells repopulate the alveolus after acute lung injury. We hypothesized that injury would initiate signals in nearby survivors. When rat ATII monolayers were wounded, elevations in intracellular free Ca²⁺ concentration ([Ca²⁺](i)) began at the edge of the wound and propagated outward as a wave for at least 300 μm. The [Ca²⁺](i) wave was due to both influx of extracellular Ca²⁺ and release of intracellular Ca²⁺ stores. Reducing Ca²⁺ influx with brief treatments of ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid or Gd³⁺ reduced both the amplitude and the apparent speed. Draining intracellular Ca²⁺ stores by pretreatment with cyclopiazonic acid eliminated the [Ca²⁺](i) wave. Therefore, the [Ca²⁺](i) wave depended critically on intracellular Ca²⁺ stores. [Ca²⁺](i) elevations propagated over a break in the monolayer, suggesting that extracellular pathways were involved. Furthermore, extracellular factors from injured cells elevated [Ca²⁺](i) in uninjured cultures. We conclude that wounding produces a [Ca²⁺](i) wave in surviving cells and part of this response is mediated by soluble factors released into the extracellular space during injury.