PULMONARY FIBROSIS CORRELATES WITH DURATION OF TISSUE NEUTROPHIL ACTIVATION

The role of inflammatory cells such as neutrophil granulocytes in the pathogenesis of pulmonary scarring is unclear. We determined the metab olic activity of neutrophils with positron emission tomography (PET) t o measure regional uptake of (F-18)-2-fluoro-2-deoxy-D-glucose ((18)FD G) following its intravenous injection. Fibrogenic or nonfibrogenic su bstances were instilled into the right upper lobe of rabbit lungs. Tim e course and intensity of the (18)FDG signal in the affected region va ried markedly, depending on the stimulus. Time to peak signal (T-max) and rate constant for its decline (k) for the test substances were, re spectively: C5a 10 h (T-max), 0.045 +/- 0.030 h(-1) (k); Streptococcus pneumoniae 15 h, 0.068 +/- 0.012 h(-1); bleomycin 28 h, 0.002 +/- 0.0 01 h(-1); microcrystalline silica (mu XSiO2), 90 h, 0.0012 +/- 0.0007 h(-1); amorphous silica (aSiO(2)), no response. Response to the nonfib rogenic agents C5a, S. pneumoniae and aSiO(2) was brief or nonexistent , falling to baseline values within 3 d, whereas that to the fibrogeni c agents bleomycin and mu XSiO2 persisted for up to 4 wk. Neutrophil n umbers in the lung were proportional to the (18)FDG signal following C 5a and S. pneumoniae, but not bleomycin and mu XSiO2. Autoradiography of lungs following administration of (H-3)-deoxyglucose [(H-3)-DC] sho wed specific localization to neutrophils in all models. Thus,(18)FDG u ptake provides a remarkably specific measure of neutrophil activity in situ, and the development of pulmonary fibrosis may be related to per sistence of this activity.