Oxygen Radicals and Arachidonate Metabolites in Lung Injury a

There is an increasing amount of evidence that oxygen radicals produced by activated phagocytic cells play an important role in the induction of acute lung injury, which in some cases leads to progressive lung injury. The bulk of work in the past several years deals with models of acute lung injury in experimental animals. The findings of many of these studies have recently been extrapolated to considerations of the adult respiratory distress syndome (ARDS) in humans. Oxygen radical production by activated phagocytic cells is now a well-known fact,' and it is known that a variety of cells, such as neutrophils, eosinophils, monocytes, and macrophages, have the ability to produce oxygen radicals upon stimulation. There is more evidence that nonphagocytic cells may, under very special circumstances, also have the ability to produce oxygen radicals? There is little evidence, however, that either platelets or basophils can, upon activation with a variety of stimuli, generate these oxygen products, even though secretion of granule products is known to occur. Oxygen radical production by phagocytic cells is stimulated by a variety of agonists. These agonists include chemotactic peptides and lipids; complement activation products such as anaphylatoxins and C3b; phorbol myristate acetate; and phagocytic stimuli including immune complexes, zymosan particles, and other insoluble materials. Cell surface interaction with any of these agonists leads to a cascade of chemical reactions which appears to initially involve activation of a cell membrane associated NADPH oxidase. This results in the progressive reduction of molecular oxygen, by a sequential addition of electrons, to a series of products, as shown in the scheme below: