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Blockade of the Fas/FasL system improves pneumococcal clearance from the lungs without preventing dissemination of bacteria to the spleen.
| Title | Blockade of the Fas/FasL system improves pneumococcal clearance from the lungs without preventing dissemination of bacteria to the spleen. |
| Publication Type | Journal Article |
| Year of Publication | 2005 |
| Authors | Matute-Bello, G, W Liles, C, Frevert, CW, Dhanireddy, S, Ballman, K, Wong, V, Green, RR, Song, HYeong, Witcher, DR, Jakubowski, JA, Martin, TR |
| Journal | J Infect Dis |
| Volume | 191 |
| Issue | 4 |
| Pagination | 596-606 |
| Date Published | 2005 Feb 15 |
| ISSN | 0022-1899 |
| Keywords | Amino Acid Substitution, Animals, Antigens, CD95, Apoptosis, Bronchoalveolar Lavage Fluid, Chemokine CXCL2, Colony Count, Microbial, Disease Models, Animal, Fas Ligand Protein, Lung, Macrophages, Male, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Monokines, Mutation, Phagocytosis, Pneumonia, Pneumococcal, Receptors, Cell Surface, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Member 6b, Spleen, Streptococcus pneumoniae, Tumor Necrosis Factor-alpha |
| Abstract | BACKGROUND: The Fas/FasL system is both proapoptotic and proinflammatory. FasL is inhibited by decoy receptor-3 (DcR3), a naturally occurring decoy receptor. We determined the effects of systemic blockade of the Fas/FasL system by a DcR3 analog (DcR3-a) in mice with pneumococcal pneumonia. METHODS: Streptococcus pneumoniae (7.2 x 105 or 1.9 x 107 cfu/mL) was instilled intratracheally into untreated C57Bl/6 mice, C57Bl/6 mice treated with DcR3-a, or Fas-deficient lpr mice, and the mice were studied 48 h later. RESULTS: After instillation of the lower bacterial dose, disruption of the Fas/FasL system by either DcR3-a or the lpr mutation resulted in improved clearance of bacteria in the lungs (mean +/- SE, 4.6+/-2.1 x 10(6) and 3.5 +/- 1.6 x 10(6) cfu/lung, respectively, vs. 21.9+/-9.3 x 10(6) cfu/lung in untreated C57Bl/6 mice; P<.05) and decreased percentage of polymorphonuclear neutrophils in bronchoalveolar lavage fluid (mean +/- SE, 19.3%+/-9.5% and 20.2%+/-7.8%, respectively, vs. 55.0%+/-12.2% in untreated C57Bl/6 mice; P<.05). These changes were associated with decreased lung concentrations of the proinflammatory cytokines tumor necrosis factor- alpha and macrophage inflammatory protein-2 and with a decrease in apoptotic cells in the alveolar walls. CONCLUSION: Blockade of the Fas/FasL system by DcR3-a in the lungs improves clearance of bacteria in mice with pneumococcal pneumonia. |
| DOI | 10.1086/427261 |
| Alternate Journal | J. Infect. Dis. |
| PubMed ID | 15655784 |
