ROLE OF ALVEOLAR MACROPHAGES IN INITIATION AND REGULATION OF INFLAMMATION IN PSEUDOMONAS-AERUGINOSA PNEUMONIA

To evaluate the role of alveolar macrophages (AMs) in acute Pseudomona s aeruginosa pneumonia in mice, AMs were depleted by aerosol inhalatio n of liposomes containing clodronate disodium. AM-depleted mice,were t hen intratracheally infected with 5 x 10(5) CFU of P, aeruginosa. In a ddition to monitoring neutrophil recruitment and chemokine releases, l ung injury was evaluated soon after infection (8 h) and at a later tim e (48 h), At 8 h, depletion of AMs reduced neutrophil recruitment, che mokine release, and lung injury. At 48 h, however, depletion of AMs de creased bacterial clearance and resulted in delayed movement of neutro phils from the site of inflammation with aggravated lung injury. With instillation of 5 x 10(7) CFU of bacteria, AM-depleted mice showed low mortality within 24 h of infection but high mortality at a later time , in contrast to non-AM-depleted mice. These results demonstrate that depletion of AMs has beneficial early effects but deleterious late eff ects on lung injury and survival in cases of P. aeruginosa pneumonia.