Role of alveolar macrophages in Candida-induced acute lung injury

Recent studies have shown that alveolar macrophages (AMs) not only act as p hagocytes but also play a central role as potent secretory cells in various lung diseases, including pneumonia and acute respiratory distress syndrome . The behavior of AMs during disseminated candidiasis, however, is insuffic iently elucidated. This study is the first to report disseminated candidias is in AM-depleted mice and to analyze the effect of AMs on Candida-induced acute lung injury. While all AM-sufficient mice died by day 2 after infecti on with Candida albicans, no mortality was observed among AM-depleted mice. Unexpectedly, the CFU numbers of C. albicans isolated from the lungs of AM -depleted mice were significantly higher than those for C. albicans isolate d from AM-sufficient mice. The lung wet-to-dry weight ratio was lower for A M-depleted mice than for AM-sufficient mice, although this difference was n ot significant. We found that bronchoalveolar lavage fluid (BALF) from AM-d epleted mice in candidemia contained fewer neutrophils than BALF from AM-su fficient mice. In addition, myeloperoxidase activities in lung homogenates of AM-depleted mice were significantly lower than those in homogenates of A M-sufficient mice. A significant decrease in levels of murine macrophage in flammatory protein 2 (MIP-2), a potent chemoattractant for neutrophils, was noted in lung homogenates from AM-depleted mice compared with levels in ho mogenates from AM-sufficient mice. Immunohistochemical studies using anti-M IP-2 antibodies revealed that AMs were the cellular source of MIP-2 within the lung during candidemia. We observed that AM depletion decreased levels of AM-derived neutrophil chemoattractant, alleviated acute lung injury duri ng candidemia, and prolonged the survival of mice in candidemia, even thoug h clearance of C. albicans from the lungs was reduced.