title: Transcytosis and surface presentation of IL-8 by venular endothelial cells.
abstract: Chemokines have been convincingly implicated in actuating inflammatory leukocyte emigration. To affect the circulating leukocytes, tissue-derived chemokines have to traverse the endothelial cells (ECs). This was thought to be accomplished by chemokine diffusion through the intercellular gaps. On the contrary, we show by electron microscopy that the prototype chemokine IL-8 is internalized by venular ECs abluminally and transcytosed to the luminal surface. Here, it is presented to the adherent leukocytes on the EC membrane, predominantly in association with the EC projections. The intact C terminus of IL-8, the molecule's "immobilization" domain, is required for the EC binding, transcytosis, and consequently, the in vivo proemigratory activity of IL-8, indicating that the described subcellular interactions of IL-8 with the ECs are functionally relevant.
authors.affiliation: Novartis Forschungsinstitut, Vienna, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Middleton
authors.forename: S
authors.initials: S
authors.lastname: Neil
authors.forename: J
authors.initials: J
authors.lastname: Wintle
authors.forename: I
authors.initials: I
authors.lastname: Clark-Lewis
authors.forename: H
authors.initials: H
authors.lastname: Moore
authors.forename: C
authors.initials: C
authors.lastname: Lam
authors.forename: M
authors.initials: M
authors.lastname: Auer
authors.forename: E
authors.initials: E
authors.lastname: Hub
authors.forename: A
authors.initials: A
authors.lastname: Rot
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism* / Q000494:pharmacology; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D014699:Venules / Q000166:cytology / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D011994:Recombinant Proteins