Acute inflammatory lung injury retards pulmonary particle clearance.

The deposition, retention, and clearance of inhaled cobalt oxide particles from the lungs of calves with acute inflammatory lung injury induced by parainfluenza-3 virus (PI-3) were examined. Acute pulmonary inflammation was induced by nebulization with 10(9) TCID50 of PI-3 virus on two successive days, and animals were subsequently exposed to an aerosol of particulate cobalt oxide (geometric mean diameter 0.54-0.65 microns) seven days post-virus infection (dpi). Pulmonary lesions at 7 dpi were typical of PI-3 pneumonitis and were characterized by patchy aveolitis and bronchiolitis with accumulations of neutrophils, macrophages, fibrin, and inflammatory debris. Calves were killed at 0, 7, and 21 days post-aerosol exposure (dpe) to evaluate particle clearance and retention by assay for cobalt in lung tissues, bronchoalveolar washings, and tracheobronchial lymph nodes. Control animals had a typically biphasic clearance pattern with rapid initial clearance of 50% of the initial lung burden (ILB) by 7 dpe followed by slower prolonged clearance. Clearance was significantly retarded (P less than 0.05) in calves with viral-induced acute inflammatory lung injury; 90% of the ILB was retained at 7 dpe. Essentially all particles recoverable by bronchoalveolar lavage were intracellular within pulmonary alveolar macrophages (PAM) in both experimental and control groups, but interstitial sequestration of particles within PAM was commonly observed only in the lungs of calves with viral pneumonitis. Pneumonic calves also exhibited retarded translocation of particles to regional lymph nodes. The results document impaired particulate clearance from acutely inflamed lungs, and implicate decreased mucociliary clearance and interstitial sequestration within PAM as the major contributing factors. These functional alterations would be expected to enhance the progression of virus-induced acute pulmonary inflammatory injury.