Blocking the ADAM9/ITGAV Pathway Ameliorates Sepsis‐Induced Acute Lung Injury by Promoting Macrophage Efferocytosis

Successfully inhibiting sepsis‐induced acute lung injury (ALI) hinges on clearing apoptotic neutrophils; however, the underlying mechanisms of this process remain elusive. In the present study, we aim to investigate how ADAM9 regulates macrophage efferocytosis during ALI. In the lipopolysaccharide (LPS)‐induced ALI mice, inhibiting ADAM9 in macrophages significantly improved ALI, simultaneously reducing the number of macrophages and neutrophils in BALF, along with a decrease in pro‐inflammatory cytokines, including IFN‐γ, iNOS, and an increase in IL‐4, IL‐10. In vitro, downregulation of ADAM9 expression in bone marrow‐derived macrophages (BMDMs) improved macrophage efferocytosis to apoptotic polymorphonuclear leukocytes (PMNs). Besides, we demonstrated that ADAM9 in BMDMs could directly bind to ITGAV in PMNs; inhibiting ITGAV expression on PMNs effectively improved ADAM9‐mediated macrophage efferocytosis. Blocking the interaction between ADAM9 and ITGAV may ameliorate sepsis‐induced ALI by promoting macrophage efferocytosis.