Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts Journal Article
| Authors: | Grassmé, H.; Jendrossek, V.; Riehle, A.; Von Kürthy, G.; Berger, J.; Schwarz, H.; Weller, M.; Kolesnick, R.; Gulbins, E. |
| Article Title: | Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts |
| Abstract: | Pseudomonas aeruginosa infection is a serious complication in patients with cystic fibrosis and in immunocompromised individuals. Here we show that P. aeruginosa infection triggers activation of the acid sphingomyelinase and the release of ceramide in sphingolipid-rich rafts. Ceramide reorganizes these rafts into larger signaling platforms that are required to internalize P. aeruglnosa, Induce apoptosis and regulate the cytokine response in infected cells. Failure to generate ceramide-enriched membrane platforms in infected cells results in an unabated inflammatory response, massive release of interleukin (IL)-1 and septic death of mice. Our findings show that ceramide-enriched membrane platforms are central to the host defense against this potentially lethal pathogen. |
| Keywords: | signal transduction; controlled study; nonhuman; mouse; mammalia; animals; mice; animal tissue; cells, cultured; apoptosis; interleukin 1beta; fluorescent dyes; animal model; enzyme activation; bacteria (microorganisms); animalia; cytokine; cystic fibrosis; cell membrane; fibroblasts; epithelial cells; host resistance; bone marrow transplantation; bacterial infection; internalization; ceramide; ceramides; sphingomyelin phosphodiesterase; mammal cell; pseudomonas aeruginosa; beta-cyclodextrins; pseudomonas; membrane microdomains; antigens, cd95; gram negative infection; nystatin; ionophores; sphingolipid; cystic fibrosis transmembrane conductance regulator; cyclodextrins; negibacteria; filipin; humans; priority journal; article; pseudomonas infections |
| Journal Title: | Nature Medicine |
| Volume: | 9 |
| Issue: | 3 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2003-03-01 |
| Start Page: | 322 |
| End Page: | 330 |
| Language: | English |
| DOI: | 10.1038/nm823 |
| PUBMED: | 12563314 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
