1. Galphai2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation.
- Author
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Pero RS, Borchers MT, Spicher K, Ochkur SI, Sikora L, Rao SP, Abdala-Valencia H, O'Neill KR, Shen H, McGarry MP, Lee NA, Cook-Mills JM, Sriramarao P, Simon MI, Birnbaumer L, and Lee JJ
- Subjects
- Allergens metabolism, Animals, Endothelium, Vascular cytology, Endotoxins metabolism, Eosinophils metabolism, Inflammation, Lung metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Neutrophils metabolism, Pertussis Toxin pharmacology, Endothelium, Vascular metabolism, GTP-Binding Protein alpha Subunit, Gi2 metabolism, Leukocytes metabolism, Signal Transduction
- 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 Galpha(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 and ex vivo studies of leukocyte trafficking demonstrated that a Galpha(i)-signaling event in endothelial cells was required for transmigration. Collectively, these data suggest that specific Galpha(i2)-mediated signaling between endothelial cells and leukocytes is required for the extravasation of leukocytes and for tissue-specific accumulation.
- Published
- 2007
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