The Role of Macrophage-derived Chemoattractant Activities in the Early Inflammatory Events of Bleomycin-induced Pulmonary Injury1–4

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Abstract
In order to explore the mechanisms that govern the entry of inflammatory cells into the injured lung, we studied the cell populations recovered by bronchoalveolar lavage of hamsters treated 1, 4, 8, and 15 days previously with a single intratracheal instillation of bleomycin or saline (airway cells), and the secretion of chemoattractant activities by these cells. These data were compared with those obtained from the cell populations set free from teased lung preparations from the same animals (lung cells). Neutrophil and lymphocyte chemoattractant activities (NCA and LCA, respectively) were assessed in culture supernatants of macrophages from airway and lung cells at all time points. Ultrastructural studies confirmed that both methods of recovering cells resulted mainly in the isolation of macrophages. The percentage of airway neutrophils was increased above that in control animals at all 4 time points, with a peak increase at Day 1; the percentage of airway lymphocytes was significantly increased above control only at Day 8. The NCA was elevated in culture medium from both airway and lung macrophages, only at Day 4 (mean ± SE, 240 ± 35 and 375 ± 57%, respectively), as compared with saline control values (119 ± 10 and 185 ± 50%, respectively) (p < 0.05); LCA was elevated from supernatants of cultured airway and lung macrophages at Day 8 (156 ± 12 and 181 ± 13%, respectively) as compared with control values (111 ± 7 and 111 ± 8%, respectively) (p < 0.05). These results suggest that the levels of airway neutrophils at Day 4 and of airway lymphocytes at Day 8 may be related to secretion of NCA and LCA by airway and lung macrophages. It is not known whether NCA and LCA are sequentially secreted by the same or by different populations of macrophages. Bleomycin was found to be chemokinetic for neutrophils but not for lymphocytes, and this property may be related to the large influx of airway neutrophils observed at Day 1.