Lung injury, inflammation, and inflammatory stimuli in rats exposed to ozone

The effects of ozone (O-3) on airway epithelia, inflammation, and expressio n of inflammatory stimuli were investigated to delineate the mechanisms of inflammatory reactions relevant to lung injury. Because the airway response s to O-3 develop gradually, this investigation included a time-sequence ana lysis. Rats exposed for 3 h to 1 ppm O-3 were studied at 4-h intervals up t o 20 h postexposure. Bronchoalveolar lavage fluid (BAL) was analyzed for al bumin as an indicator of increased permeability, polymorphonuclear leukocyt es (PMNs) to assess the inflammatory status, macrophage inflammatory protei n-2 (MIP-ZI an inflammatory chemokine), and cell adhesion molecules for the ir role in inflammation and PMN functions. The time-related increase in alb umin was matched by a similar significant increase for PMNs, MIP-2, and int ercellular adhesion molecule-1 (ICAM-1). However, no marked change occurred for beta-2 integrin (CD-18) and leukotriene B-4 (LTB4). The results establ ish a temporal correlation of epithelial permeability with changes in infla mmatory activity and stimuli responsible for PMN recruitment in the lung. T he observations of elevated MIP-2 and ICAM-1 levels are consistent with the ir role in injury and inflammation. An early expression of MIP-2 mRNA in BA I cells, that is, immediately post O-3 exposure, and the peak increase in B AI MIP-2 levels 4 h later support the chemotactic role of h MIP-2 in PMN re cruitment at 4- and 12-h time points. The rapid drop in MIP-2 and ICAM-1 le vels appears to signal the termination of inflammatory cell recruitment whi ch is accompanied by an onset of recovery.