Gαi2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation

Abstract

The trafficking of leukocytes from the blood to sites of inflammation is the cumulative result of receptor-ligand-mediated signaling events associated with the leukocytes themselves as well as with the underlying vascular endothelium. Our data show that Gα_i signaling pathways in the vascular endothelium regulate a critical step required for leukocyte diapedesis. In vivo studies using knockout mice demonstrated that a signaling event in a non-lymphohematopoietic compartment of the lung prevented the recruitment of proinflammatory leukocytes. Intravital microscopy showed that blockade was at the capillary endothelial surface andex vivo studies of leukocyte trafficking demonstrated that a Gα_i-signaling event in endothelial cells was required for transmigration. Collectively, these data suggest that specific Gα_i2-mediated signaling between endothelial cells and leukocytes is required for the extravasation of leukocytes and for tissue-specific accumulation.