Targeting Gα₁₃-integrin interaction ameliorates systemic inflammation.

ABSTRACT: 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 Gα₁₃-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 Gα₁₃ knockout inhibited septic thrombosis whereas leukocyte Gα₁₃ knockou

SUBMITTER: Cheng N 

PROVIDER: S-EPMC8159967 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature