title: 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.
authors.affiliation: Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA.
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Pero
authors.forename: Michael T
authors.initials: MT
authors.lastname: Borchers
authors.forename: Karsten
authors.initials: K
authors.lastname: Spicher
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Ochkur
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Sikora
authors.forename: Savita P
authors.initials: SP
authors.lastname: Rao
authors.forename: Hiam
authors.initials: H
authors.lastname: Abdala-Valencia
authors.forename: Katie R
authors.initials: KR
authors.lastname: O'Neill
authors.forename: Huahao
authors.initials: H
authors.lastname: Shen
authors.forename: Michael P
authors.initials: MP
authors.lastname: McGarry
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Lee
authors.forename: Joan M
authors.initials: JM
authors.lastname: Cook-Mills
authors.forename: P
authors.initials: P
authors.lastname: Sriramarao
authors.forename: Melvin I
authors.initials: MI
authors.lastname: Simon
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D000485:Allergens / Q000378:metabolism; D000818:Animals; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004731:Endotoxins / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000378:metabolism*; D007249:Inflammation; D007962:Leukocytes / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D000485:Allergens; D004731:Endotoxins; D037342:Pertussis Toxin; D051960:GTP-Binding Protein alpha Subunit, Gi2