Platelets Protect Against Murine Pneumonia

Platelets have been called “ancient granulocytes” because they are capable of recognizing and destroying microbial invaders through their release of a variety of anti-microbial proteins. Experimental evidence indicates that this may involve direct platelet-microbial interactions or occur indirectly through platelet-leukocyte interactions, neutrophil histone-platelet interactions and/or platelet-directed neutrophil extracellular trap formation. To test the hypothesis that platelets contribute to innate lung immunity, we examined the clinical course, lung histopathology and pathogen burden of mice -/+ antibody-mediated platelet depletion who were subjected to aerosolized bacteria (Streptococcus pneumoniae or Pseudomonas aeruginosa). Mice (C57BL/6, 10 weeks) were injected by tail vein with a purified rat monoclonal antibody directed against mouse GpIbα (or control antibody) resulting in platelet depletion to ~ 20% at 3 hours that persisted for 48 hours. 30 minutes after GpIbα antibody injection mice were placed into a closed system for 60 minutes where they were exposed to 10 ml nebulized S. pneumoniae (2-6 x 10¹¹ CFU/ml) or P. aeruginosa (1-4 x 10¹⁰ CFU/ml). All platelet depleted animals infected with S. pneumoniae died by day 4 after infection, whereas all platelet replete mice survived the infection. Infection with P. aeruginosa resulted in death of all animals, although the platelet replete mice lived longer than the platelet depleted mice. No platelet depleted sham-infected animals died. The lungs of animals were harvested, fixed and prepared for histopathology with hematoxylin and eosin staining; or harvested, homogenized and plated for bacterial CFU measurements. Whole lungs of platelet-depleted and infected mice were congested. Histopathology showed increased red cells in the venules of platelet-depleted S. pneumoniae-infected mice but no difference in air-space hemorrhage in comparison with platelet-depleted sham-infected lungs and platelet-replete S. pneumoniae-infected lungs. Platelet depletion resulted in ~ 5-fold increase in lung S. pneumoniae CFUs and ~ 10-fold increase in P. aeruginosa CFUs. These results indicate that platelets provide defense against pneumonia. The mechanism of this effect is not known. Experiments are ongoing to determine if it is a consequence of platelet-dependent hemostasis, platelet-leukocyte interactions and/or direct platelet-microbial interactions leading to the release of bactericidal compounds.