title: IL-4 and IL-13 downregulate rolling adhesion of leukocytes to IL-1 or TNF-alpha-activated endothelial cells by limiting the interval of E-selectin expression.
abstract: Leukocyte extravasation is governed by the endothelium, expressing a defined pattern of adhesion molecules in response to inflammatory stimuli. Among them, E-selectin, which is expressed in response to interleukin 1 (IL-1) or tumour necrosis factor alpha (TNF-alpha), provides rolling adhesion of the circulating leukocytes, a transient and reversible interaction that initiates leukocyte extravasation. In our experiments, E-selectin expression culminated after 4 to 6 h and declined thereafter. After 24 h a considerable amount of E-selectin was presented, reflecting its continuous expression in different inflammatory skin disorders. After preincubation of the endothelial cells with TNF-alpha together with IL-4 or IL-13, E-selectin mRNA transcription and protein expression were markedly reduced at 8 h and almost abolished at 20 h. In contrast, early E-selectin expression between 2 to 6 h was not significantly impaired. In a rotating adherence assay that mimics physiological shear forces in circulation, preincubation of the endothelial cells with TNF-alpha for 4 and 20 h induced similar adherence of neutrophils, which was largely E-selectin dependent. According to the modified expression kinetics of E-selectin in the presence of IL-4 of IL-13 rolling adhesion was unimpaired at 4 h but significantly diminished after 20 h of preincubation. Similar results were obtained with clones of the cutaneous T cell lymphoma cell line HUT78 highly expressing the E-selectin ligand cutaneous lymphocyte-associated Ag. Together, these data suggest that IL-4 and IL-13 control the rolling adhesion by limiting the period of the induced E-selectin expression and may thereby confine the acute phase of leukocyte emigration.
authors.affiliation: Institute of Toxicology of the Swiss Federal Institute of Technology and University of Zurich, CH-8603 Schwerzenbach, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Etter
authors.forename: R
authors.initials: R
authors.lastname: Althaus
authors.forename: H P
authors.initials: HP
authors.lastname: Eugster
authors.forename: L F
authors.initials: LF
authors.lastname: Santamaria-Babi
authors.forename: L
authors.initials: L
authors.lastname: Weber
authors.forename: R
authors.initials: R
authors.lastname: Moser
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D019040:E-Selectin / Q000276:immunology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D019040:E-Selectin; D007375:Interleukin-1; D018793:Interleukin-13; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D015847:Interleukin-4