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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.<\/jats:p>","DOI":"10.1128\/iai.01579-06","type":"journal-article","created":{"date-parts":[[2007,2,13]],"date-time":"2007-02-13T01:18:37Z","timestamp":1171329517000},"page":"1586-1597","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":65,"title":["Influence of Neutropenia on the Course of Serotype 8 Pneumococcal Pneumonia in Mice"],"prefix":"10.1128","volume":"75","author":[{"given":"Matthew","family":"Marks","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamika","family":"Burns","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Abadi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Albert Einstein College of Medicine and Jacobi Medical Center, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beza","family":"Seyoum","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Thornton","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Tuomanen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liise-anne","family":"Pirofski","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York"},{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.6.2862-2866.1999"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1006\/mpat.1997.0185"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.7.3823-3828.2004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-60-5-759"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830111013"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.2.448-455.1995"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.3.912-922.1998"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.57.7.2037-2042.1989"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.2.788-794.2004"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12035"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.1.325-333.2005"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.8.4530-4538.2005"},{"key":"e_1_3_2_14_2","first-page":"353","year":"2001","unstructured":"Burns, T., Z. 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