The Function of Lung and Blood Neutrophils in Patients with the Adult Respiratory Distress Syndrome: Implications for the Pathogenesis of Lung Infections

Abstract

Pulmonary infections are a frequent cause of morbidity and mortality in patients with the adult respiratory distress syndrome (ARDS), but the reason is uncertain. Because neutrophils are important for lung defense and are found in increased numbers in the bronchoalveolar lavage fluid of patients with ARDS, we compared the functional activities of neutrophils obtained from lavage fluid and pulmonary artery blood of 28 patients shortly after the onset of ARDS. The lavage fluids contained 81.3 +/- 9.9% neutrophils, of which more than 95% were viable by vital dye exclusion, and the total protein concentrations were increased (98.8 +/- 98.5 mg/dl). The production of superoxide anion and hydrogen peroxide by the neutrophils in lavage fluid was significantly impaired compared with simultaneously tested pulmonary artery and normal neutrophils, and the microbicidal activity of the lavage neutrophils for Staphylococcus aureus was significantly impaired. The migration of alveolar neutrophils in response to a variety of stimuli was markedly reduced as compared with both pulmonary artery and normal neutrophils. The alterations in superoxide anion production and chemotaxis could be reproduced by exposure of normal neutrophils to oxidants (glucose:glucose oxidase), but not to other mediators that have been found in ARDS lavage fluids. Although the pulmonary artery neutrophils from the same patients had impaired production of superoxide anion and hydrogen peroxide, their microbicidal activity and chemotactic responses were normal. These findings indicate that the function of alveolar neutrophils is impaired in the lungs of patients with ARDS. This could contribute to the high incidence of pulmonary infections in these patients.

Oncostatin M Production by Blood and Alveolar Neutrophils during Acute Lung Injury

“…The five patients who had low but detectable levels of plasma OSM all had septic shock, as previously reported (Guillet et al, 1995). However, blood PMN are known to be activated during severe pneumonia, as reflected by the results of several functional tests based on adhesion, degranulation, and the oxidative burst (Chabot et al, 1998;CholletMartin et al, 1996;Martin et al, 1991). Our results thus suggest that PMN are not globally activated in these settings, but that certain functions are selectively activated.…”

“…Spontaneous high OSM production may serve as a new marker of cell activation in this setting. Indeed, alveolar PMN are known to be locally activated, as reflected by CD11b and CD62L adhesion molecule expression and ROS production (Chabot et al, 1998;Chollet-Martin et al, 1996;Martin et al, 1991). PMN may thus have a dual role, both inducing and helping to repairing tissue lesions.…”

“…Interest in the pathogenetic mechanisms of ALI has focused in recent years on interactions between PMN and cytokines (Pittet et al, 1997). In particular, several reports from our group and others have indicated that circulating and alveolar PMN are activated and that proinflammatory cytokines may play an active role in this process (Chollet-Martin et al, 1992Martin et al, 1991). Activated PMN can damage the lung through several potential mechanisms, including the release of proteases, cytokines, and reactive oxygen species (ROS), but recent data also suggest a role for PMN in the modulation of inflammation and tissue repair (Boutten et al, 1998;Donnelly et al, 1995).…”

Longevity of augmented phagocytic activity of heterophils in neonatal chickens following administration ofSalmonella enteritidis-immune lymphokines to chickens

“…Unlike the finite period of heterophil activation demonstrated in this study, neutrophils have been associated with chronic inflammatory proccesses resulting in serious consequences for the host. In Adult Respiratory Syndrome (ARDS) (Martin et al, 1991), the killing activity of neutrophils is downregulated as a protective mechanism by the host in response to large numbers of these cells and the tissue damage done by discharge of particular enzymes contained within the cell. Due to the prolonged recovery period of individuals afflicted by ARDS, decreases in neutrophil function contribute to overwhelming pulmonary infections so often seen (Martin et al, 1991).…”

“…In Adult Respiratory Syndrome (ARDS) (Martin et al, 1991), the killing activity of neutrophils is downregulated as a protective mechanism by the host in response to large numbers of these cells and the tissue damage done by discharge of particular enzymes contained within the cell. Due to the prolonged recovery period of individuals afflicted by ARDS, decreases in neutrophil function contribute to overwhelming pulmonary infections so often seen (Martin et al, 1991). We presently have no definitive evidence supporting tissue damage or destruction as a result of ILK-mediated heterophil activity during the first week post-hatch (Kogut et al, 1996).…”