Figure 8.

Effect of agonistic anti-DR5 mAb therapy on survival and alveolar macrophage apoptosis of mice challenged with S. pneumoniae. Wild-type mice were either left untreated (A) or were made neutropenic by i.p. injection of neutrophil-depleting 1A8 antibody (B) applied at −12 h and −2 h before infection with S. pneumoniae (10⁷ CFU/mouse and 3–4 × 10⁶ CFU/mouse, respectively). 6 h after infection, mice received a single intratracheal application of control IgG or agonistic anti-DR5 mAb (MD5-1; 75 µg/mouse), and survival (n = 10 mice per group) was recorded over time. Data in A and B are representative of two to three independent experiments. (C–F) WT mice were infected with S. pneumoniae (5 × 10⁶ CFU/mouse). 6 h after infection, mice either received a single intratracheal instillation of control IgG (white bars) or agonistic anti-DR5 antibody MD5-1 (75 µg/mouse; black bars). At 24 h after infection, induction of apoptosis was analyzed in resident alveolar macrophages (C) and exudate macrophages (D) by flow cytometry, and respective bacterial loads were determined at 24 and 72 h after infection both in BAL fluids (E) and lung tissue (F), as indicated. The data in (C-F) are shown as mean ± SEM of n = 3 mice per time point and treatment group and are representative of two independent experiments with similar results. *, P < 0.05; **, P < 0.01, relative to control IgG.