Inflammatory Cells are Sources of Polyamines that Induce Alveolar Macrophage to Undergo Apoptosis During Pneumocystis Pneumonia

Abstract

PNEUMOCYSTIS is an opportunistic fungal pathogen that causes pneumonia in immunocompromised individuals such as patients with AIDS. Alveolar macrophages are critical in the clearance of Pneumocystis organisms. However, the number of alveolar macrophages is decreased by approximately 60% during Pneumocystis pneumonia (PcP) (Lasbury, Durant, and Lee 2003). One mechanism that reduces the alveolar macrophage number is apoptosis (Lasbury et al. 2006). High concentrations of polyamines are known to induce apoptosis, and we have found that the levels of some polyamines (spermidine, acetylspermine, and acetylspermidine) are greatly increased in Pneumocystis-infected lungs and that these polyamines can induce normal alveolar macrophages to undergo apoptosis. We also have found that bronchoalveolar lavage (BAL) fluids from Pneumocystis-infected animals can induce apoptosis in normal alveolar macrophages, but this apoptosis-inducing ability of the BAL fluid is lost when the polyamines are depleted. These results suggest that high polyamine levels induce apoptosis in alveolar macrophages during PcP. Pneumocystis organisms produce and excrete polyamines (Chin et al. 1996), but it is unknown whether host cells also produce polyamines during PcP. To identify cells that produce polyamines during Pneumocystis infection, we examined the differential expression of ornithine decarboxylase (ODC), a key enzyme on the production of polyamines. We also investigated the uptake of polyamines by alveolar macrophages from Pneumocystis-infected rats.