Early production of tumor necrosis factor-alpha by Gr-1 cells and its role in the host defense to pneumococcal infection in lungs.
In this study, we elucidated the role of tumor necrosis factor (TNF)-alpha in the host defense to pulmonary infection with Streptococcus pneumoniae and defined the cellular source of this cytokine at an early stage of infection. Administration of anti-TNF-alpha monoclonal antibody (mAb) resulted in the reduced accumulation of neutrophils in bronchoalveolar lavage fluids (BALFs) and severe exacerbation of this infection. In a flow cytometric analysis, the intracellular expression of TNF-alpha was detected in Gr-1(bright+) and Gr-1(dull+) cells during the time intervals postinfection, and F4/80(+) cells expressed intracellular TNF-alpha before Gr-1(dull+) cells appeared. The Gr-1(bright+) and Gr-1(dull+) cells sorted from BALF cells at 24 h were identified as neutrophils and macrophage-like cells, respectively, and the Gr-1(dull+) cells expressing CD11c, partially CD11b and a marginal level of F4/80 secreted TNF-alpha in in vitro cultures. Finally, deletion of Gr-1(+) cells by administration of the specific mAb significantly reduced the concentrations of this cytokine in BALF at 6 and 12 h postinfection, but not the expression of TNF-alpha in F4/80(+) cells. Thus, these results demonstrated that neutrophils, F4/80(+) macrophages and Gr-1(dull+) CD11c(+) macrophage-like cells played an important role in the production of TNF-alpha in lungs at an early stage of infection with S. pneumoniae.
Hatta
Masumitsu
M
Department of Infection Control, Tohoku University Graduate School of Medicine, Sendai, Japan.
Yamamoto
Natsuo
N
Miyazato
Akiko
A
Ishii
Naoto
N
Nakamura
Kiwamu
K
Inden
Ken
K
Aoyagi
Tetsuji
T
Kunishima
Hiroyuki
H
Hirakata
Yoichi
Y
Suzuki
Kazuo
K
Kaku
Mitsuo
M
Kawakami
Kazuyoshi
K
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004815:Epidermal Growth Factor / Q000032:analysis; D005434:Flow Cytometry; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology; D011956:Receptors, Cell Surface / Q000032:analysis*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology*
C464944:Emr4 protein, mouse; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C551746:granulocyte receptor 1, mouse; D004815:Epidermal Growth Factor