PAF, ceramide and pulmonary edema: alveolar flooding and a flood of questions

Lung edema commonly occurs in human diseases. One form involves increased vascular permeability and the flooding of protein-rich edema fluid into the alveoli, and is a major component of lethal syndromes of acute lung injury. The molecular mechanisms are incompletely characterized. A recent study using experimental models identified a previously unrecognized pathway to lung edema that involved the inflammatory phospholipid platelet-activating factor (PAF), ceramide (a cell-associated lipid) and acid sphingomyelinase (an enzymatic intermediate). This mechanism, which acts in concert with lung cyclooxygenases, might provide new therapeutic targets, but unknown aspects of the signaling cascades need to be resolved.