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Galphai2-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 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.

SUBMITTER: Pero RS 

PROVIDER: S-EPMC1838609 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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Galphai2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation.

Pero Ralph S RS   Borchers Michael T MT   Spicher Karsten K   Ochkur Sergei I SI   Sikora Lyudmila L   Rao Savita P SP   Abdala-Valencia Hiam H   O'Neill Katie R KR   Shen Huahao H   McGarry Michael P MP   Lee Nancy A NA   Cook-Mills Joan M JM   Sriramarao P P   Simon Melvin I MI   Birnbaumer Lutz L   Lee James J JJ  

Proceedings of the National Academy of Sciences of the United States of America 20070307 11


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 prev  ...[more]

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