Enhanced immediate inflammatory response to Streptococcus pneumoniae in the lungs of mice with pulmonary emphysema.
OBJECTIVE
Pulmonary emphysema is associated with frequent respiratory infections but little is known about the reasons for this susceptibility to bacterial infection. We previously demonstrated an impaired inflammatory response to Streptococcus pneumoniae in an experimental emphysema mouse model at 24 h, or longer following bacterial inoculation. Toll-like receptors (TLR) have been recognized as regulators in the inflammatory response. We examined the expression of TLR on alveolar macrophages in experimental emphysema mice and evaluated the immediate inflammatory response of the emphysematous lung to streptococcal infection.


METHODS
Elastase was administered once into mice trachea to induce pulmonary emphysema. Three weeks later, expression of TLR-2 and TLR-4 in the BAL cells was examined by immunostaining. Following the intratracheal inoculation of Streptococcus pneumoniae, pro-inflammatory cytokine concentrations were measured in the BAL fluids of the control and emphysema mice.


RESULTS
The expression of TLR-2 and TLR-4 was significantly elevated in the alveolar macrophages of emphysema mice. Six hours after infection, neutrophils in the BAL fluid of emphysema mice were significantly increased, and the levels of tumour necrosis factor-alpha, IL-1beta and IL-6 were significantly elevated, compared with the control mice. At 3 h post inoculation, macrophage inflammatory protein-2 levels were significantly elevated.


CONCLUSIONS
The immediate inflammatory response in the emphysematous lung is significantly enhanced in response to streptococcal infection. This may be partly attributed to the increased expression of TLR in the alveolar macrophages of emphysema mice.
Tokairin
Yoshikane
Y
Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
Shibata
Yoko
Y
Sata
Makoto
M
Abe
Shuichi
S
Takabatake
Noriaki
N
Igarashi
Akira
A
Ishikawa
Tomomi
T
Inoue
Sumito
S
Kubota
Isao
I
D000818:Animals; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000473:pathology; D010196:Pancreatic Elastase / Q000009:adverse effects; D011008:Pneumococcal Infections / Q000378:metabolism* / Q000382:microbiology; D011014:Pneumonia / Q000378:metabolism* / Q000382:microbiology; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000378:metabolism* / Q000382:microbiology; D013296:Streptococcus pneumoniae; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; D015850:Interleukin-6; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D010196:Pancreatic Elastase