Pathogenesis of pneumococcal pneumonia in cyclophosphamide-induced leukopenia in mice.
Streptococcus pneumoniae pneumonia frequently occurs in leukopenic hosts, and most patients subsequently develop lung injury and septicemia. However, few correlations have been made so far between microbial growth, inflammation, and histopathology of pneumonia in specific leukopenic states. In the present study, the pathogenesis of pneumococcal pneumonia was investigated in mice rendered leukopenic by the immunosuppressor antineoplastic drug cyclophosphamide. Compared to the immunocompetent state, cyclophosphamide-induced leukopenia did not hamper interleukin-1 (IL-1), IL-6, macrophage inflammatory protein-1 (MIP-1), MIP-2, and monocyte chemotactic protein-1 secretion in infected lungs. Leukopenia did not facilitate bacterial dissemination into the bloodstream despite enhanced bacterial proliferation into lung tissues. Pulmonary capillary permeability and edema as well as lung injury were enhanced in leukopenic mice despite the absence of neutrophilic and monocytic infiltration into their lungs, suggesting an important role for bacterial virulence factors and making obvious the fact that neutrophils are ultimately not required for lung injury in this model. Scanning and transmission electron microscopy revealed extensive disruption of alveolar epithelium and a defect in surfactant production, which were associated with alveolar collapse, hemorrhage, and fibrin deposits in alveoli. These results contrast with those observed in immunocompetent animals and indicate that leukopenic hosts suffering from pneumococcal pneumonia are at a higher risk of developing diffuse alveolar damage.
Infectious Diseases Research Center, Laval University, Quebec City, Canada G1V 4G2.
Erjian
E
Wang
Marie
M
Simard
Nathalie
N
Ouellet
Yves
Y
Bergeron
Denis
D
Beauchamp
Michel G
MG
Bergeron
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D002199:Capillary Permeability; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D003520:Cyclophosphamide / Q000009:adverse effects; D004195:Disease Models, Animal; D004487:Edema; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology; D007970:Leukopenia / Q000139:chemically induced / Q000150:complications / Q000276:immunology / Q000473:pathology*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D011018:Pneumonia, Pneumococcal / Q000150:complications / Q000276:immunology / Q000473:pathology*; D015996:Survival Rate
D018906:Antineoplastic Agents, Alkylating; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D007375:Interleukin-1; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D003520:Cyclophosphamide