No abstract

Accumulation of monocytes and neutrophils and fibrous distortion of the airway are characteristics of airway disease secondary to smoking. The presence of inflammatory cells and fibrosis correlate, and, therefore, we postulated that lung fibroblasts might release chemotactic activity for neutrophils and monocytes in response to smoke extract. To test this hypothesis, human fetal lung (HFL1) fibroblasts were cultured, and the supernatant fluid was evaluated for neutrophil (NCA) and monocyte (MCA) chemotactic activities with a blind well chamber technique. HFL1 fibroblasts released chemotactic activity in response to smoke extract in a dose- and time-dependent manner (P < 0.05). Checkerboard analysis showed that the activity was predominantly chemotactic. Partial characterization of the released chemotactic activity revealed that the activity was partly heat labile, trypsin sensitive, and ethyl acetate extractable. Lipoxygenase inhibitors and cycloheximide inhibited the release of both NCA and MCA. Molecular-sieve chromatography revealed that NCA and MCA were heterogeneous. NCA was inhibited by anti-human interleukin (IL)-8 and anti-granulocyte colony-stimulating factor antibodies and a leukotriene (LT) B(4)-receptor antagonist. Anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) and anti-monocyte chemoattractant protein (MCP)-1 antibodies and an LTB(4)-receptor antagonist inhibited MCA. Immunoreactive IL-8, granulocyte colony-stimulating factor, GM-CSF, and MCP-1 significantly increased in culture supernatant fluid in response to smoke extract. Finally, smoke extract augmented the expression of mRNAs of IL-8, GM-CSF, and MCP-1. These data demonstrate that lung fibroblasts release NCA and MCA in response to smoke extract and suggest that lung fibroblasts may modulate the inflammatory cell recruitment into the lung.

To clarify the structure and function of the airways in Mycobacterium avium-intracellulare (MAI) infection, we performed pulmonary function tests and high-resolution computed tomography (HRCT) of the thorax in female patients 61 +/- 9 yr of age (n = 12) with pulmonary MAI infection without predisposing lung disease and compared their data with those of normal female volunteers 54 +/- 8 yr of age (n = 9). We calculated the E/I ratio, i.e., the average ratio of HRCT number at full expiration to that at full inspiration, as an index for the evaluation of air trapping distal to the small airways. Patients showed significant increases in residual volume and slope of phase III (DeltaN2) of the single-breath nitrogen test, and significant decreases in flow at 50 and 25% of FVC, suggesting hyperinflation and obstruction of the small airways. HRCT of patients revealed the small nodules and ectasis of bronchioles and small bronchi located mainly in segments (S) S2, S3, S4, and S5. The E/I ratio was significantly elevated in patients, and especially higher in the upper lung field than in the lower lung field, suggesting air trapping distal to the small airways. The difference of E/I ratio between the upper and lower field is probably related to the segmental distribution of CT abnormalities. These findings suggest that MAI infection can lead to air trapping distal to the small airways.

stimulates lung epithelial cells to release neutrophil and monocyte chemotactic activities. Am. J. Physiol. 276 (Lung Cell. Mol. Physiol. 20): L941-L950, 1999.-Although bleomycin, an antineoplastic drug, is used in the treatment of a variety of tumors, the mechanisms of bleomycin-induced lung injury and fibrosis are not fully elucidated. We postulated that bleomycin might stimulate A549 cells, a type II pneumocyte cell line, to release neutrophil and monocyte chemotactic activities (NCA and MCA, respectively). To test this hypothesis, A549 cell supernatant fluids were harvested and evaluated for NCA and MCA. A549 cell supernatant fluids showed NCA and MCA in response to bleomycin in a dose-and time-dependent manner (P Ͻ 0.05). Checkerboard analysis revealed that both NCA and MCA were predominantly chemotactic. Partial characterization of the released NCA and MCA showed that the activities were partially heat labile, trypsin digested, and predominantly ethyl acetate extractable. Lipoxygenase inhibitors and cycloheximide inhibited the release of chemotactic activities significantly. Molecular-sieve column chromatography revealed that the released activities were heterogeneous. However, lowmolecular-weight activity was prominent. Leukotriene B 4receptor antagonist, anti-interleukin-8, anti-granulocyte colony-stimulating factor, and anti-monocyte chemoattractant protein-1 antibodies attenuated the chemotactic activities. Immunoreactive leukotriene B 4 receptor, interleukin-8, granulocyte colony-stimulating factor, and monocyte chemoattractant protein-1 significantly increased in supernatant fluids in response to bleomycin. These data demonstrate that bleomycin stimulates type II epithelial cells to release chemotactic activities and plays a role in inflammatory cell recruitment into the lung.