Exclusive neutrophil recruitment with oncostatin M in a human system.
Oncostatin M (OSM), a member of the IL-6 family has been postulated to be a potent recruiter of leukocytes, however information regarding the molecular mechanism(s) underlying this event is extremely limited. Therefore, the aim of this study was to investigate the role of OSM-mediated leukocyte recruitment in a human system in vitro under flow conditions. A parallel-plate flow chamber assay was used to examine leukocyte recruitment from whole blood by human umbilical vein endothelium treated for 24 hours with OSM. OSM in a dose-response manner revealed very significant leukocyte rolling and adhesion reaching optimal levels at a very low concentration of OSM (10 ng/ml). The OSM-induced leukocyte rolling and adhesion was comparable to levels seen with tumor necrosis factor. OSM was extremely selective for neutrophil recruitment (96%) with <3% lymphocyte recruitment. By contrast, tumor necrosis factor-alpha revealed no such selectivity, recruiting 70% neutrophils and at least 25% lymphocytes and detectable levels of eosinophils at 24 hours. The molecular mechanism underlying the leukocyte recruitment seemed to be entirely dependent on P-selectin as leukocyte recruitment could be completely blocked by the addition of a P-selectin-blocking antibody. An elevation in both P-selectin message and protein was observed with 24 hours of OSM stimulation of endothelium. By contrast, E-selectin and VCAM-1 were not detectable after OSM stimulation. Similar results were seen with passaged dermal microvascular endothelium that does not have a prestored pool of P-selectin. Based on these results, we conclude that OSM may be a very selective potent recruiter of neutrophils in more prolonged inflammatory conditions, an event exclusively dependent on P-selectin.
Kerfoot
S M
SM
Department of Physiology and Biophysics, Immunology Research Group, University of Calgary, Calgary, Alberta, Canada.
Raharjo
E
E
Ho
M
M
Kaur
J
J
Serirom
S
S
McCafferty
D M
DM
Burns
A R
AR
Patel
K D
KD
Kubes
P
P
D001790:Blood Physiological Phenomena; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D020556:Neutrophil Infiltration / Q000502:physiology*; D053683:Oncostatin M; D019007:P-Selectin / Q000378:metabolism; D010455:Peptides / Q000502:physiology*; D010477:Perfusion; D014471:Umbilical Veins; D015854:Up-Regulation
C508351:OSM protein, human; D019007:P-Selectin; D010455:Peptides; D053683:Oncostatin M