i2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation

Ralph S. Pero, Michael T. Borchers, Karsten Spicher, Sergei I. Ochkur, Lyudmila Sikora, Savita P. Rao, Hiam Abdala-Valencia, Katie R. O'Neill, Huahao Shen, Michael P. McGarry, Nancy A. Lee, Joan M. Cook-Mills, P. Sriramarao, Melvin I. Simon, Lutz Birnbaumer, James J. Lee

Research output: Contribution to journalArticle

47 Scopus citations

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 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 and ex vivo studies of leukocyte trafficking demonstrated that a Gαi-signaling event in endothelial cells was required for transmigration. Collectively, these data suggest that specific Gαi-mediated signaling between endothelial cells and leukocytes is required for the extravasation of leukocytes and for tissue-specific accumulation.

Original languageEnglish (US)
Pages (from-to)4371-4376
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number11
DOIs
StatePublished - Mar 13 2007

Keywords

  • G proteins
  • Inflammation
  • Knockout mice
  • Leukocyte trafficking
  • Pulmonary models

ASJC Scopus subject areas

  • General

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    Pero, R. S., Borchers, M. T., Spicher, K., Ochkur, S. I., Sikora, L., Rao, S. P., Abdala-Valencia, H., O'Neill, K. R., Shen, H., McGarry, M. P., Lee, N. A., Cook-Mills, J. M., Sriramarao, P., Simon, M. I., Birnbaumer, L., & Lee, J. J. (2007). i2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation. Proceedings of the National Academy of Sciences of the United States of America, 104(11), 4371-4376. https://doi.org/10.1073/pnas.0700185104