Absence of the endothelial oxidase AOC3 leads to abnormal leukocyte traffic in vivo.
Leukocyte migration from the blood to tissues is a prerequisite for normal immune responses. We produced mice deficient in an endothelial cell-surface oxidase (amine oxidase, copper containing-3 [AOC3], also known as vascular adhesion protein-1 [VAP-1]) and found that this enzyme is needed for leukocyte extravasation in vivo. Real-time imaging shows that AOC3 mediates slow rolling, firm adhesion, and transmigration of leukocytes in vessels at inflammatory sites and lymphoid tissues. Absence of AOC3 results in reduced lymphocyte homing into lymphoid organs and in attenuated inflammatory response in peritonitis. These data alter the paradigm of leukocyte extravasation cascade by providing the first physiological proof for the concept that endothelial cell surface enzymes regulate the development of inflammatory reactions in vivo and suggest that this enzyme should be useful as an anti-inflammatory target.
Stolen
Craig M
CM
Department of Medical Microbiology, MediCity Research Laboratory, National Public Health Institute, Turku University, 20520 Turku, Finland.
Marttila-Ichihara
Fumiko
F
Koskinen
Kaisa
K
Yegutkin
Gennady G
GG
Turja
Raisa
R
Bono
Petri
P
Skurnik
Mikael
M
Hänninen
Arno
A
Jalkanen
Sirpa
S
Salmi
Marko
M
D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D002450:Cell Communication; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000378:metabolism; D004195:Disease Models, Animal; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D007962:Leukocytes / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010538:Peritonitis / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism
D015815:Cell Adhesion Molecules; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing); C492678:semicarbazide-sensitive amine oxidase-vascular adhesion protein-1, mouse