Transcytosis and surface presentation of IL-8 by venular endothelial cells

J. Middleton, S. Neil, I. Clark-Lewis, H. Moore, L. Charles, M. Auer, H. Elin, R. Antal, J. Wintle

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)385-395
Number of pages11
JournalCell
Volume91
Issue number3
DOIs
Publication statusPublished - 31 Oct 1997

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