The damage to pulmonary alveolar epithelial cells that occurs in many inflammatory conditions is thought to be caused in part by phagocytic neutrophils. To investigate this process, we exposed monolayers of purified rat alveolar epithelial cells to stimulated human neutrophils and measured cytotoxicity using a "Crrelease assay. We found that stimulated neutrophils killed epithelial cells by a process that did not require neutrophil-generated reactive oxygen metabolites. Pretreatment of neutrophils with an antibody (anti-Mol) that reduced neutrophil adherence to epithelial cells limited killing. Although a variety of serine protease inhibitors partially inhibited cytotoxicity, we found that neutrophil cytoplasts, neutrophil lysates, neutrophil-conditioned medium, purified azurophilic or specific granule contents, and purified human neutrophil elastase did not duplicate the injury. We conclude that stimulated neutrophils can kill alveolar epithelial cells in an oxygen metabolite-independent manner. Tight adherence of stimulated neutrophils to epithelial cell monolayers appears to promote epithelial cell killing.

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Hypoxemia usually accompanies acute pulmonary embolism in humans, but its mechanism remains poorly understood. We studied 2 patients with acute, massive pulmonary embolism (APE) documented by pulmonary angiography. Both patients had a markedly increased alveolar-arterial oxygen difference (AaPO2). The technique of multiple inert gas elimination was used to determine the distribution of ventilation-perfusion ratios (VA/Q). An increase in VA/Q inequality was found in both patients, but this increased inequality was caused entirely by an increase in the ventilation of lung units with high VA/Q ratio. No blood flow was found perfusing lung units with a VA/Q ratio of less than 1.0. Both patients, however, had a large amount of blood flow (20 and 39% of the cardiac output) perfusing unventilated lung units (shunt), and the percent of minute ventilation to unperfused lung units as well as the VD/VT determined from the Bohr equation were increased. We conclude that in these 2 patients with APE, VA/Q inequality did not play a major role in their hypoxemia and that the widened AaPO2 is explained by the large shunts that were found.

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