| First Author | Grassmé H | Year | 2017 |
| Journal | Cell Host Microbe | Volume | 21 |
| Issue | 6 | Pages | 707-718.e8 |
| PubMed ID | 28552668 | Mgi Jnum | J:272682 |
| Mgi Id | MGI:6284973 | Doi | 10.1016/j.chom.2017.05.001 |
| Citation | Grassme H, et al. (2017) beta1-Integrin Accumulates in Cystic Fibrosis Luminal Airway Epithelial Membranes and Decreases Sphingosine, Promoting Bacterial Infections. Cell Host Microbe 21(6):707-718.e8 |
| abstractText | Chronic pulmonary colonization with bacterial pathogens, particularly Pseudomonas aeruginosa, is the primary cause of morbidity and mortality in patients with cystic fibrosis (CF). We observed that beta1-integrins accumulate on the luminal membrane of upper-airway epithelial cells from mice and humans with CF. beta1-integrin accumulation is due to increased ceramide and the formation of ceramide platforms that trap beta1-integrins on the luminal pole of bronchial epithelial cells. beta1-integrins downregulate acid ceramidase expression, resulting in further accumulation of ceramide and consequent reduction of surface sphingosine, a lipid that kills bacteria. Interrupting this vicious cycle by triggering surface beta1-integrin internalization via anti-beta1-integrin antibodies or the RGD peptide ligand-or by genetic or pharmacological correction of ceramide levels-normalizes beta1-integrin distribution and sphingosine levels in CF epithelial cells and prevents P. aeruginosa infection in CF mice. These findings suggest a therapeutic avenue to ameliorate CF-associated bacterial infections. |
