title: Neutrophil and monocyte adherence to and migration across monolayers of cytokine-activated endothelial cells: the contribution of CD18, ELAM-1, and VLA-4.
abstract: Pretreatment of endothelial cells with cytokines enhances the adherence of leukocytes, a process that is mediated by surface proteins expressed on both cell types. A three-dimensional model system for the simultaneous determination of leukocyte adherence and migration was used to study the contribution of CD11/CD18, endothelial leukocyte-adhesion molecule-1 (ELAM-1) and VLA-4 in neutrophil and monocyte adherence to and migration through cytokine-activated endothelial cells. Pretreatment of endothelial cells for 4 hours with recombinant interleukin-1 beta (rIL-1 beta) was found to enhance neutrophil adherence and migration to a much greater extent than monocyte adherence and migration. Neutrophil adherence was almost completely prevented by the combined use of monoclonal antibodies (MoAbs) against ELAM-1 and CD18. Although ELAM-1 has been designated an endothelial cell-specific cytokine-inducible receptor for neutrophils, we observed that ENA2, an anti-ELAM-1 MoAb, significantly reduced monocyte adherence about 30%. MoAbs against VLA-4, the ligand of the cytokine-inducible receptor VCAM-1, did not affect monocyte adherence. However, the combined use of the MoAbs against CD18, ELAM-1, and VLA-4 had a very strong and additive inhibitory effect on rIL-1 beta-induced monocyte adherence. The anti-CD18 MoAb reduced both rIL-1 beta-induced neutrophil and monocyte migration far below the level of the unstimulated controls, whereas neither the anti-ELAM-1 nor the anti-VLA-4 MoAb significantly affected the process of migration. Our results indicate that neutrophils and monocytes initially adhere to cytokine-activated endothelial cells by CD18-independent and (to a lesser extent) by CD18-dependent mechanisms and subsequently change gears to a completely CD18-dependent migratory mechanism.
authors.affiliation: Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
authors.forename: B C
authors.initials: BC
authors.lastname: Hakkert
authors.forename: T W
authors.initials: TW
authors.lastname: Kuijpers
authors.forename: J F
authors.initials: JF
authors.lastname: Leeuwenberg
authors.forename: J A
authors.initials: JA
authors.lastname: van Mourik
authors.forename: D
authors.initials: D
authors.lastname: Roos
mesh_terms: D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology*; D016029:Receptors, Very Late Antigen / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D014471:Umbilical Veins
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007375:Interleukin-1; D016028:Receptors, Leukocyte-Adhesion; D016029:Receptors, Very Late Antigen; D011994:Recombinant Proteins; D003094:Collagen