FUNCTIONAL AND METABOLIC-ACTIVITY OF GRANULOCYTES FROM PATIENTS WITH ADULT RESPIRATORY-DISTRESS SYNDROME - EVIDENCE FOR ACTIVATED NEUTROPHILS IN THE PULMONARY CIRCULATION

Abstract

The circulating granulocyte (PMN) may be an effector cell that causes pulmonary vascular injury in the adult respiratory distress syndrome (ARDS), the functional status of PMN from patients with this disorder has not been previously defined. PMN in samples of pulmonary artery blood from patients with ARDS are in a functionally and metabolically activated state. The mean chemotactic index of PMN from ARDS patients was 172 .+-. 22 SEM [standard error of the mean] compared with a mean chemotactic index of 79 .+-. 8 of of PMN from normal subjects (P = 0.0001), a 227 .+-. 24% increase over the control value. Respiratory burst activity of PMN, as assessed by the chemiluminescence response (CL), was 151 .+-. 12% of control (mean peak CL of PMN from patients with ARDS, 166 .+-. 31 cpm .times. 103; mean peak CL of normal PMN, 105 .+-. 16 cpm .times. 103; P = 0.04), suggesting that granulocytes from patients with ARDS are likely to generate increased quantities of active O2 metabolites when stimulated. The chemotactic and chemiluminescence responses of PMN from patients with ARDS were much greater than those of critically ill patients without ARDS, were enhanced in the absence of concurrent bacterial infection, and did not appear to be blunted by recent administration of glucocorticoids. The PMN from patients with ARDS had increased ratios of intracellular cGMP to cAMP (165 .+-. 5% of control, P = 0.0002), which may be related to the enhanced metabolic activity. Release of superoxide anion, a potential mediator of endothelial injury, was increased over that of control by PMN from 4 of 8 patients with ARDS (mean, 205 .+-. 71% of normal). The circulating PMN is apparently in an activated state in patients with ARDS and may be more likely to release active O2 species and other inflammatory mediators when perturbed, potentially contributing to pulmonary vascular injury and alveolitis.