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 molecula r mechanism(s) underlying this event is extremely limited. Therefore, the a im. of this study was to investigate the role of OSM-mediated leukocyte rec ruitment in a human system in vitro under flow conditions. A parallel-plate flow chamber assay was used to examine leukocyte recruitment from whole bl ood by human umbilical vein endothelium treated for 24 hours with OSM. OSM in a dose-response manner revealed very significant leukocyte rolling and a dhesion reaching optimal levels at a very low concentration of OSM (10 ng/m l). The OSM-induced leukocyte rolling and adhesion was comparable to levels seen with tumor necrosis factor. OSM was extremely selective for neutrophi l recruitment (96%) with < 3% lymphocyte recruitment. By contrast, tumor ne crosis factor-a revealed no such selectivity, recruiting 70% neutrophils an d 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 complet ely 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 s timulation of endothelium. By contrast, E-selectin and VCAM-1 were not dete ctable after OSM stimulation. Similar results were seen with passaged derma l microvascular endothelium that does not have a prestored pool of P-select in. Based on these results, we conclude that OSM may be a very selective po tent recruiter of neutrophils in more prolonged inflammatory conditions, an event exclusively dependent on P-selectin.