Figure 6.
Vascular integrity during pneumosepsis partly depends on platelet GPVI, but CLEC 2 or neutrophils are not crucially involved. Mice were injected with JAQ1, INU-1, or IgG control antibody or platelet-depleting antibody with or without depletion of neutrophils, infected with K pneumoniae via the airways, and sacrificed after 12, 36, or 42 hours after infection. (A-F) Panels show lung bleeding. (A) Representative photographs of infected lungs. Lung bleeding early after infection (t = 12; B-C) or at late-stage pneumosepsis (t = 36; D-F). (B,D) Hemoglobin was measured in 50-fold-diluted lung homogenates by light density at 410 nm optical density (OD). (C,E) Lung bleeding was scored on hematoxylin and eosin–stained tissue sections by a pathologist blinded for groups. (F) Representative photomicrographs of hematoxylin and eosin–stained lung sections of uninfected and infected mice at 36 hours. (i-iv) 40× enlarged pictures of uninfected mice receiving IgG control (i), 36-hour-infected IgG control (ii), JAQ1-treated mice (iii), or mice with a <1% platelet count due to aGPIb antibody (iv). Bleeding is indicated by an arrow. Data are presented as box and whisker plots of 8 mice per group at each time point. In panel E, all platelet-depleted mice had the maximal bleeding score (4). *P < .05, **P < .005, ***P < .0005, and ****P < .00005 vs IgG control.