| First Author | Cheng N | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 3185 |
| PubMed ID | 34045461 | Mgi Jnum | J:341997 |
| Mgi Id | MGI:6713979 | Doi | 10.1038/s41467-021-23409-0 |
| Citation | Cheng N, et al. (2021) Targeting Galpha13-integrin interaction ameliorates systemic inflammation. Nat Commun 12(1):3185 |
| abstractText | Systemic inflammation as manifested in sepsis is an excessive, life-threatening inflammatory response to severe bacterial or viral infection or extensive injury. It is also a thrombo-inflammatory condition associated with vascular leakage/hemorrhage and thrombosis that is not effectively treated by current anti-inflammatory or anti-thrombotic drugs. Here, we show that MB2mP6 peptide nanoparticles, targeting the Galpha13-mediated integrin "outside-in" signaling in leukocytes and platelets, inhibited both inflammation and thrombosis without causing hemorrhage/vascular leakage. MB2mP6 improved mouse survival when infused immediately or hours after onset of severe sepsis. Furthermore, platelet Galpha13 knockout inhibited septic thrombosis whereas leukocyte Galpha13 knockout diminished septic inflammation, each moderately improving survival. Dual platelet/leukocyte Galpha13 knockout inhibited septic thrombosis and inflammation, further improving survival similar to MB2mP6. These results demonstrate that inflammation and thrombosis independently contribute to poor outcomes and exacerbate each other in systemic inflammation, and reveal a concept of dual anti-inflammatory/anti-thrombotic therapy without exacerbating vascular leakage. |
