title: Monocyte modulation of endothelial leukocyte adhesion molecules.
abstract: Leukocyte adhesion to endothelium is dependent on expression of specialized molecules. Several of these molecules are upregulated by cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). We investigated the effect of medium conditioned by unstimulated (MCM) or stimulated monocytes and of recombinant cytokines on endothelial adhesion receptor expression. IL-1 beta, TNF-alpha, and MCM induced E-selectin similarly, whereas MCM induced VCAM-1 and ICAM-1 to a lesser extent than did TNF-alpha, and MCM induced VCAM-1 only weakly. The addition of pentoxifylline (10(-3) mol/L) to monocytes during MCM preparation blocked TNF-alpha production but not that of IL-1 beta or IL-6, and it reduced IL-1ra significantly (p < 0.05). When the MCM was devoid of TNF-alpha or when TNF-alpha was neutralized with a specific antibody, the action of MCM on E-selectin expression was significantly lower. Anti-IL-1 beta decreased the activity of MCM on endothelial E-selectin expression by about 50%. The effect of MCM on adhesion molecules was accompanied by an increase in monocyte adhesion. Inhibition of TNF-alpha production reduced monocytes adhesion slightly but significantly (18%, p < 0.05), whereas anti-IL-1 beta antibody decreased adhesion by 48% (p < 0.001). These results show that adherent monocytes released cytokines and antagonists that affect leukocyte adhesion receptors on endothelium differently from recombinant cytokines. E-selectin expression--and to a lesser extent ICAM expression--is modified, resulting in a modulation of leukocyte adhesion to endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Laboratoire de Biologie Vasculaire et Cellulaire, Université de Paris VII, France.
authors.forename: D
authors.initials: D
authors.lastname: Weill
authors.forename: J L
authors.initials: JL
authors.lastname: Wautier
authors.forename: C
authors.initials: C
authors.lastname: Dosquet
authors.forename: M P
authors.initials: MP
authors.lastname: Wautier
authors.forename: M P
authors.initials: MP
authors.lastname: Carreno
authors.forename: B
authors.initials: B
authors.lastname: Boval
mesh_terms: D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000494:pharmacology*; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000032:analysis / Q000096:biosynthesis*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D007700:Kinetics; D007962:Leukocytes / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D010431:Pentoxifylline / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D016207:Cytokines; D019040:E-Selectin; C507763:IL1RN protein, human; D016023:Integrins; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D010431:Pentoxifylline