The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/11/1757/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 9, November 2, 1998 1757-1762

Brief Definitive Reports

Endothelial Cell "Memory" of Inflammatory Stimulation: Human Venular Endothelial Cells Store Interleukin 8 in Weibel-Palade Bodies

Barbara Wolff*, Alan R. Burns{ddagger}, James Middleton*, and Antal Rot*

From the * Novartis Forschungsinstitut, A-1235 Vienna, Austria; and the {ddagger} Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas 77030-2600

The expression and secretion of interleukin (IL)-8, the prototype member of the C-X-C subfamily of chemokines, can be induced by diverse inflammatory stimuli in many cells, including endothelial cells (EC). Upon de novo synthesis, IL-8 localizes intracellularly in the Golgi apparatus, from where it is secreted. In addition to this constitutive secretory pathway, we describe a depot storage and separate regulated secretory pathway of IL-8 in EC.

The prolonged stimulation of primary human EC with inflammatory mediators resulted in the accumulation of IL-8 in Weibel-Palade bodies, where it colocalized with von Willebrand factor. IL-8 was retained in these storage organelles for several days after the removal of the stimulus and could be released by EC secretagogues such as phorbol myristate acetate, the calcium ionophore A23187, and histamine. These findings suggest that storage of IL-8 in Weibel-Palade bodies may serve as the EC "memory" of a preceding inflammatory insult, which then enables the cells to secrete IL-8 immediately without de novo protein synthesis.

Key Words: interleukin 8 • endothelial cell • inflammation • Weibel-Palade bodies • secretion

Address correspondence to Barbara Wolff, Novartis Forschungsinstitut, Brunner Strasse 59, A-1235 Vienna, Austria. Phone: 43-1-86634-275; Fax: 43-1-86634-354; E-mail: barbara.wolff-winiski{at}pharma.novartis.com

A.R. Burns was supported by the Methodist Hospital Foundation, the Chao Fellowship, and the National Institutes of Health (grant HL42550).

J. Middleton's present address is Department of Rheumatology, Orthopaedic and District Hospital, Oswestry S710 7A6, UK.


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