Open AccessGα i2 -mediated signaling events in the endothelium are involved in controlling leukocyte extravasation
Author(s) -
Ralph Pero,
Michael T. Borchers,
Karsten Spicher,
Sergei I. Ochkur,
Lyudmila Sikora,
Savita P. Rao,
Hiam AbdalaValencia,
K.R. O'Neill,
Huahao Shen,
Michael P. McGarry,
Nancy A. Lee,
Joan M. CookMills,
P. Sriramarao,
Melvin I. Simon,
Lutz Birnbaumer,
James J. Lee
Publication year - 2007
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0700185104
Subject(s) - extravasation , leukocyte extravasation , endothelium , microbiology and biotechnology , inflammation , signal transduction , intravital microscopy , endothelial stem cell , biology , cell signaling , immunology , proinflammatory cytokine , in vivo , in vitro , endocrinology , biochemistry
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 Gαi 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 Gαi -signaling event in endothelial cells was required for transmigration. Collectively, these data suggest that specific Gαi2 -mediated signaling between endothelial cells and leukocytes is required for the extravasation of leukocytes and for tissue-specific accumulation.