Leukotriene B4 (LTB4) is a major product of human alveolar macrophages and has potent chemotactic activity for neutrophils (PMN) in vitro. To evaluate the effects of LTB4 in the normal human lung, we instilled LTB4 (5 X 10-7M, 10 ml) into a subsegment of the right middle lobe and 0.9% NaCI (10 ml) into a subsegment of the lingula using a fiberoptic bronchoscope in 12 healthy human volunteers. 4 h later, we performed bronchoalveolar lavage of the same subsegments. Compared with the NaCl instillation, LTB4 caused a large increase in lavage total cells (NaCI = 6.8±1.0 X 106 vs. LTB4 = 26.4±5.0 X 106, P < 0.01), most of which were PMN (NaCl = 12.2±4.6% vs. LTB4 = 55.7±6.0%, P < 0.001). In contrast, there was only a small increase in lavage total protein, and the lavage total protein correlated weakly with lavage total cells and PMN. The production of superoxide anion by the lavage PMN in response to phorbol myristate acetate was similar to that of peripheral blood PMN. The migration of lavage PMN was normal toward the chemotactic peptide FMLP, but reduced toward LTB4 and zymosan-activated human serum. Morphometric analysis using transmission electron microscopy indicated a selective loss of small granules in the lung neutrophils as compared with peripheral blood neutrophils. The data indicate that in the normal human lung, LTB4 can recruit active PMN into the airspaces without causing a significant change in the protein permeability of the epithelial barrier.

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.