Influence of neutropenia on the course of serotype 8 pneumococcal pneumonia in mice.
Polymorphoneutrophils (PMNs) are important effector cells in host defense against pneumonia. However, PMNs can also induce inflammation and tissue damage. To investigate the contribution of PMNs to host defense against pneumococcal pneumonia, we determined the effect of the PMN-depleting rat monoclonal antibody RB6-8C5 (RB6) on survival and inflammatory and cellular response in the lungs to a lethal intranasal infection with a serotype 8 pneumococcus in BALB/c mice. Control mice received rat immunoglobulin G (rIgG). Strikingly, the survival of RB6-treated mice was significantly prolonged compared to that of rIgG-treated mice. Although the numbers of CFU in the lungs were statistically similar in both groups 4, 24, and 32 h after infection, rIgG-treated mice developed higher levels of bacteremia, and histopathological examination of the lungs of infected mice revealed marked differences between RB6- and rIgG-treated mice. RB6-treated mice had focal, perivascular lesions without accompanying parenchymal inflammation, and rIgG-treated mice had diffuse, interstitial parenchymal inflammation. Lung homogenates from the rIgG-treated mice had more leukocytes and significantly more total and apoptotic PMNs as determined by fluorescence-activated cell sorter analysis with Annexin V and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling staining of lung tissue samples. Studies with a pneumolysin-deficient mutant of the serotype 8 strain we used also demonstrated the prolonged survival of RB6- compared to rIgG-treated mice. Taken together, our findings suggest that PMNs enhance the likelihood of early death and alter the pathological response to pneumococcal lung infection in BALB/c mice with serotype 8 pneumonia without significantly affecting bacterial clearance or the cytokine response.
Marks
Matthew
M
Division of Infectious Diseases, Albert Einstein College of Medicine, Forchheimer Bldg., 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Burns
Tamika
T
Abadi
Maria
M
Seyoum
Beza
B
Thornton
Justin
J
Tuomanen
Elaine
E
Pirofski
Liise-anne
LA
D000818:Animals; D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis; D016470:Bacteremia; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D001769:Blood / Q000382:microbiology; D018925:Chemokines / Q000032:analysis; D015169:Colony Count, Microbial; D016207:Cytokines / Q000032:analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D006651:Histocytochemistry; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007958:Leukocyte Count; D047589:Leukocyte Reduction Procedures; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009503:Neutropenia / Q000150:complications*; D009504:Neutrophils / Q000502:physiology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013301:Streptolysins / Q000235:genetics
D017304:Annexin A5; D001426:Bacterial Proteins; D018925:Chemokines; D016207:Cytokines; D004269:DNA, Bacterial; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae