Galphai2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation.
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.
Pero
Ralph S
RS
Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA.
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
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
D000485:Allergens; D004731:Endotoxins; D037342:Pertussis Toxin; D051960:GTP-Binding Protein alpha Subunit, Gi2