Am. J. Respir. Crit. Care Med., Volume 158, Number 2, August 1998, 620-628

Pulmonary Fibrosis Correlates with Duration of Tissue Neutrophil Activation

HAZEL A. JONES, JOHN B. SCHOFIELD, THOMAS KRAUSZ, ALAN R. BOOBIS, and CHRISTOPHER HASLETT

National Heart and Lung Institute, Departments of Medicine and Histopathology, Imperial College School of Medicine, London; and Respiratory Medicine Unit, University of Edinburgh, Royal Infirmary, Edinburgh, United Kingdom

The role of inflammatory cells such as neutrophil granulocytes in the pathogenesis of pulmonary scarring is unclear. We determined the metabolic activity of neutrophils with positron emission tomography (PET) to measure regional uptake of (¹⁸F)-2-fluoro-2-deoxy-D-glucose (¹⁸FDG) following its intravenous injection. Fibrogenic or nonfibrogenic substances were instilled into the right upper lobe of rabbit lungs. Time course and intensity of the ¹⁸FDG signal in the affected region varied markedly, depending on the stimulus. Time to peak signal (T_max) and rate constant for its decline (k) for the test substances were, respectively: C5a 10 h (T_max), 0.045 ± 0.030 h¹ (k); Streptococcus pneumoniae 15 h, 0.068 ± 0.012 h¹; bleomycin 28 h, 0.002 ± 0.001 h¹; microcrystalline silica (µXSiO₂), 90 h, 0.0012 ± 0.0007 h¹; amorphous silica (aSiO₂), no response. Response to the nonfibrogenic agents C5a, S. pneumoniae and aSiO₂ was brief or nonexistent, falling to baseline values within 3 d, whereas that to the fibrogenic agents bleomycin and µXSiO₂ persisted for up to 4 wk. Neutrophil numbers in the lung were proportional to the ¹⁸FDG signal following C5a and S. pneumoniae, but not bleomycin and µXSiO₂. Autoradiography of lungs following administration of (³H)-deoxyglucose [(³H)-DG] showed specific localization to neutrophils in all models. Thus, ¹⁸FDG uptake provides a remarkably specific measure of neutrophil activity in situ, and the development of pulmonary fibrosis may be related to persistence of this activity.

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