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Among the different mechanisms involved, polymorphonuclear leukocytes (PMNs) may play a central role in the pathogenesis of adult respiratory distress syndrome (ARDS). PMNs were evaluated in 15 patients with ARDS, in 21 at risk of developing ARDS (AR), and in 36 controls (C). Spontaneous and opsonized zymosan (OZ), phorbol myristate acetate (PMA), and F-Met-Leu-Phe (F-M-L-P)-stimulated oxygen radical production was measured by luminol- and lucigenin-enhanced chemiluminescence (CL). Spontaneous CL activity of PMNs from ARDS patients was significantly greater than that from the PMN control (luminol CL, 2.8 +/- 0.6 vs. 0.8 +/- 0.1 mV, p less than 0.001; lucigenin CL, 2.0 +/- 0.6 vs. 0.30 +/- 0.04 mV, p less than 0.001), and the CL value from AR patients (luminol CL, 1.3 +/- 0.2 mV, p less than 0.001 vs. C; lucigenin CL, 0.8 +/- 0.1 mV, p less than 0.001 vs. C) was found to be between the ARDS and C patients. The peak of PMA-stimulated CL occurred earlier and it was significantly higher in ARDS patients than in AR patients (p less than 0.05) and controls (p less than 0.001). When the CL response was elicited with F-M-L-P, no difference among the three groups was found. When stimulated with OZ, the peak CL generated by PMNs from ARDS patients was significantly depressed compared with controls (luminol CL, 26.7 +/- 1.8 vs. 40.9 +/- 2.3 mV, p less than 0.01; lucigenin CL, 5.0 +/- 0.4 vs. 7.4 +/- 0.5 mV, p less than 0.005) with a similar result being obtained from AR patients (luminol CL, 32.1 +/- 2.5 mV, p less than 0.01 vs. C). Plasma from ARDS and AR patients showed a defective opsonizing capacity, suggesting in vivo complement consumption in both patient groups. No correlation between the severity of hypoxemia, the cause of ARDS, the outcome, and the different PMN functions could be established. Our results are in agreement with a determinant role of PMNs in the development of ARDS. The opposite metabolic responses may explain both the pulmonary injury and the increased susceptibility to infections observed in patients at risk of or with ARDS.