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G{alpha}i2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation

Pero, Ralph S. and Borchers, Michael T. and Spicher, Karsten and Ochkur, Sergei I. and Sikora, Ludmila and Rao, Savita P. and Abdala-Valencia, Hiam and O'Neill, Katie R. and Shen, Huahao and McGarry, Michael P. and Lee, Nancy A. and Cook-Mills, Joan M. and Sriramarao, P. and Simon, Melvin I. and Birnbaumer, Lutz and Lee, James J. (2007) G{alpha}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). pp. 4371-4376. ISSN 0027-8424. PMCID PMC1838609. doi:10.1073/pnas.0700185104.

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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 G{alpha}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 G{alpha}i-signaling event in endothelial cells was required for transmigration. Collectively, these data suggest that specific G{alpha}i2-mediated signaling between endothelial cells and leukocytes is required for the extravasation of leukocytes and for tissue-specific accumulation.

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Additional Information:© 2007 by The National Academy of Sciences of the USA Contributed by Melvin I. Simon, January 9, 2007 (received for review November 14, 2006) Published online before print March 7, 2007, 10.1073/pnas.0700185104 We thank numerous individuals, including Dana Colbert, Tracy L. Ansay, Edith M. Hines, Travis Biechele, and Alfred D. Doyle. We also thank the Mayo Clinic Arizona Core facilities (Histology, Lisa Barbarisi; Immunology, Tammy Brehm-Gibson; Mouse Special Animal Services, Suresh Savarirayan; Medical Graphic Arts, Marv Ruona; Video Production and Services, Randall J. Raish; Research Library Services, Joseph Esposito). In addition, we thank our administrative staff, Linda Mardel and Margaret (Peg) McGarry. This work was supported in part by the Mayo Foundation and grants from the National Institutes of Health to J.J.L. (HL065228 and K26-RR019709), N.A.L. (HL058723), J.M.C.-M. (HL68171), P.S. (AI35796 and HL079304), M.I.S. (GM34236), and L.B. (DK-19318). Author contributions: R.S.P., M.T.B., S.I.O., N.A.L., M.I.S., L.B., and J.J.L. designed research; R.S.P., M.T.B., S.I.O., L.S., S.P.R., H.A.-V., K.R.O., H.S., and M.P.M. performed research; K.S., L.S., S.P.R., H.A.-V., J.M.C.-M., P.S., M.I.S., and L.B. contributed new reagents/analytic tools; R.S.P., M.T.B., S.I.O., H.S., M.P.M., N.A.L., J.M.C.-M., P.S., M.I.S., and J.J.L. analyzed data; and R.S.P., M.T.B., J.M.C.-M., P.S., M.I.S., and J.J.L. wrote the paper. The authors declare no conflict of interest. This article contains supporting information online at
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Subject Keywords:G proteins, inflammation, knockout mice, leukocyte trafficking, pulmonary models
Issue or Number:11
PubMed Central ID:PMC1838609
Record Number:CaltechAUTHORS:PERpnas07
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8759
Deposited By: Archive Administrator
Deposited On:13 Sep 2007
Last Modified:08 Nov 2021 20:52

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