Targeting β1-integrin inhibits vascular leakage in endotoxemia

Abstract

Significance Compromised vascular integrity is associated with capillary leakage in sepsis, but effective therapies stabilizing the vasculature are lacking. Here, we show that targeting β1-integrin in vivo with inhibitory antibodies or deletion of a single allele of endothelial β1-integrin inhibits lipopolysaccharide (LPS)-induced vascular leakage in murine endotoxemia. The inflammatory agents IL-1β, thrombin, and LPS induced changes in endothelial cell–extracellular matrix (ECM) adhesion via β1-integrin, angiopoietin-2, and the adapter protein tensin-1, leading to increased endothelial cell contractility and permeability. These results indicate that β1-integrin actively promotes vascular leakage and that targeting β1-integrin signaling could be a novel means of achieving vascular stabilization in pathological vascular leak.