Detection of paracrine factors in oxidant lung injury

It is well recognized that the oxidant gases ozone and nitrogen dioxide cause lung injury at high concentrations and, as such, are considered to be "hazardous" air pollutants. What is not known is the upper limit of their concentration in ambient air that can be tolerated without causing lung injury. This uncertainty is due, in major part, to a lack of sensitive and noninvasive tests that can identify the presence of early lung injury after exposure to oxidant gases. The hypothesis underlying the studies reported in this document was that the changes in cell populations that occur in the lung after oxidant lung injury are due to the local generation of lung-cell-specific growth factors, and that these factors should leak into the blood stream in sufficient quantities to allow their identification. Once identified, such factors could be used as early markers of oxidant injury. The question asked in the design of these studies was: "Is oxidant lung injury associated with the appearance in blood of factors that enhance lung cell growth, as tested in a cultured lung cell bioassay?" Groups of rats were exposed to either 1 ppm ozone, 85 percent oxygen, or air, and samples of plasma, lung washings, and lung tissue were collected at intervals over a two-week period. These samples were tested for their effect on the DNA synthesis of purified populations of three major lung cell types (pneumocyte, fibroblast, and endothelial cell) in culture. The concentrations of the two oxidant gases used in these studies were selected on the basis of their known effect on these cell types in the intact animal. The collected samples were tested either whole or after separation into various fractions, determined by the preference of the sample's constituents for an alkaline or acidic environment. This fractionation procedure was included because simple testing of crude samples may not always reveal the presence of biologically active material because both growth stimulators and growth inhibitors may be present in the same sample. The results from testing whole samples confirm that factors that enhance DNA synthesis by all three lung cell types do appear in blood and lavage after exposure to 1 ppm ozone or 85 percent oxygen. These factors appear to be distinct for each lung cell type, in that the timing of maximal activity in the collected samples differs for each cell type. The time at which they appear in blood bears a close temporal relationship with cellular changes reported to occur in the whole lung of similarly exposed animals.(ABSTRACT TRUNCATED AT 400 WORDS)