title: Endothelium-derived GM-CSF influences expression of oncostatin M.
abstract: During and after transendothelial migration, neutrophils undergo a number of phenotypic changes resulting from encounters with endothelium-derived factors. This report uses an in vitro model with human umbilical vein endothelial cells and isolated human neutrophils to examine the effects of two locally derived cytokines, granulocyte (G)-macrophage (M) colony-stimulating factor (GM-CSF) and G-CSF, on oncostatin M (OSM) expression. Neutrophils contacting activated HUVEC expressed and released increased amounts of oncostatin M (OSM), a proinflammatory cytokine known to induce polymorphonuclear neutrophil adhesion and chemotaxis. Neutrophil transendothelial migration resulted in threefold higher OSM expression and protein levels compared with nontransmigrated cells. Addition of anti-GM-CSF neutralizing antibody reduced OSM expression level but anti-G-CSF was without effect. GM-CSF but not G-CSF protein addition to cultures of isolated neutrophils resulted in a significant increase in OSM protein secretion. However, inhibition of β(2) integrins by neutralizing antibody significantly reduced GM-CSF-induced OSM production indicating this phenomenon is adhesion dependent. Thus cytokine-stimulated endothelial cells can produce sufficient quantities of GM-CSF to influence in an adhesion-dependent manner, the phenotypic characteristics of neutrophils resulting in the latter's transmigration. Both transmigration and adhesion phenomenon lead to increased production of OSM by neutrophils that then play a major role in inflammatory response.
authors.affiliation: Department of Pathology, Laboratory Medicine, King Hussein Cancer Center, Amman, Jordan. wbjeirami@khcc.jo
authors.forename: Wafa M
authors.initials: WM
authors.lastname: Elbjeirami
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Donnachie
authors.forename: Alan R
authors.initials: AR
authors.lastname: Burns
authors.forename: C Wayne
authors.initials: CW
authors.lastname: Smith
mesh_terms: D057134:Antibodies, Neutralizing; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D042783:Endothelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D009504:Neutrophils / Q000502:physiology*; D053683:Oncostatin M / Q000235:genetics / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D018821:CD18 Antigens; D017077:Culture Media, Conditioned; D053683:Oncostatin M; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor