title: Adhesion promotes transcellular leukotriene biosynthesis during neutrophil-glomerular endothelial cell interactions: inhibition by antibodies against CD18 and L-selectin.
abstract: Eicosanoid formation by transcellular routes can amplify the levels and types of lipid mediators within a local milieu. To evaluate the role of adhesion in this process, we assessed the influence of mAb against adhesion molecules on LTC4 generation by PMN-endothelial cell interaction. Transcellular LTC4 generation was initiated by addition of fMLP to coincubations of GM-CSF-primed PMN and TNF-activated endothelial cells cultured from kidney glomeruli. Both PMN-endothelial cell adhesion and transcellular LTC4 generation were inhibited by mAb against leukocyte L-selectin and CD18. These results indicate that cytokine-treated PMN and endothelial cells generate LTC4 via transcellular routes by receptor-triggered mechanisms. They suggest that adhesion promotes transcellular eicosanoid biosynthesis and that adhesion molecules may also be targets for blockade of transcellular biosynthesis of lipid mediators.
authors.affiliation: Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115.
authors.forename: H R
authors.initials: HR
authors.lastname: Brady
authors.forename: C N
authors.initials: CN
authors.lastname: Serhan
mesh_terms: D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D018821:CD18 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D002450:Cell Communication; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000098:blood supply; D007700:Kinetics; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D016028:Receptors, Leukocyte-Adhesion / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013189:SRS-A / Q000096:biosynthesis*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016028:Receptors, Leukocyte-Adhesion; D011994:Recombinant Proteins; D013189:SRS-A; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor