Pneumococcus-induced granulocytopenia and pulmonary leukostasis in rabbits

Mortality associated with pneumococcal disease often remains unexplained. Intraperitoneal inoculation of live PNCs into rabbits induced significant granulocytopenia compared with broth-injected controls (p < 0.001). Lung sections from the infected rabbits had significantly increased mean alveolar septal wall granulocytes compared with controls (p < 0.01). Granulocytopenia and pulmonary leukostasis occurred only in those animals with high levels of bacteremia. Intravenous challenge of rabbits with sonified, nonviable PNCs induced a mean change of blood granulocytes of -64% compared with +124% for saline-injected controls, a difference significant at p < 0.001. Mean lung granulocytes from the PNC sonicate-challenged animals were 10.7 +/- 1.7 cells/HPF compared with 4.0 +/- 1.4 for controls, a difference significant at p < 0.001. Pulmonary vascular granulocyte plugging was found in five of six experimental animals but in none of six controls. complement-depleted animals displayed significantly less granulocytopenia (p < 0.005) and pulmonary leukostasis (p < 0.005). Therefore PNC constituents induce profound, possibly complement-mediated granulocytopenia and pulmonary leukostasis. Similar phenomena may contribute to the pulmonary dysfunction and even death associated with human pneumococcal disease.