| First Author | Dagvadorj J | Year | 2015 |
| Journal | Immunity | Volume | 42 |
| Issue | 4 | Pages | 640-53 |
| PubMed ID | 25862090 | Mgi Jnum | J:229700 |
| Mgi Id | MGI:5753016 | Doi | 10.1016/j.immuni.2015.03.007 |
| Citation | Dagvadorj J, et al. (2015) Lipopolysaccharide Induces Alveolar Macrophage Necrosis via CD14 and the P2X7 Receptor Leading to Interleukin-1alpha Release. Immunity 42(4):640-53 |
| abstractText | Acute lung injury (ALI) remains a serious health issue with little improvement in our understanding of the pathophysiology and therapeutic approaches. We investigated the mechanism that lipopolysaccharide (LPS) induces early neutrophil recruitment to lungs and increases pulmonary vascular permeability during ALI. Intratracheal LPS induced release of pro-interleukin-1alpha (IL-1alpha) from necrotic alveolar macrophages (AM), which activated endothelial cells (EC) to induce vascular leakage via loss of vascular endothelial (VE)-cadherin. LPS triggered the AM purinergic receptor P2X7(R) to induce Ca(2+) influx and ATP depletion, which led to necrosis. P2X7R deficiency significantly reduced necrotic death of AM and release of pro-IL-1alpha into the lung. CD14 was required for LPS binding to P2X7R, as CD14 neutralization significantly diminished LPS induced necrotic death of AM and pro-IL-1alpha release. These results demonstrate a key role for pro-IL-1alpha from necrotic alveolar macrophages in LPS-mediated ALI, as a critical initiator of increased vascular permeability and early neutrophil infiltration. |
