The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/11/1751/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 9, November 2, 1998 1751-1756

Brief Definitive Reports

Rapid Secretion of Prestored Interleukin 8 from Weibel-Palade Bodies of Microvascular Endothelial Cells

Jon Olav Utgaard*, Frode L. Jahnsen*, Arne Bakka{ddagger}, Per Brandtzaeg*, and Guttorm Haraldsen*

From the * Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology, and the {ddagger} Surgical Department B, University of Oslo, The National Hospital, Rikshospitalet, N-0027 Oslo, Norway

Interleukin (IL)-8, a C-X-C chemokine, activates integrin-mediated adhesion of neutrophils. Presentation of IL-8 on the endothelial cell surface may promote leukocyte extravasation. We found that cultured human microvascular endothelial cells from the intestine (HIMEC) and from nasal polyps (PMEC), but not human umbilical vein endothelial cells (HUVEC), contained IL-8 in intracellular granules that coexpressed von Willebrand factor (vWf ). This observation was corroborated by the immunohistochemical observation of double-positive granules (IL-8+vWf+) in vessels of small and large intestine, nasal mucosa, and skin, whereas umbilical cords revealed no endothelial IL-8. After treatment of HIMEC or PMEC with histamine or thrombin, a dramatic increase in supernatant IL-8 concentration was observed within 3 min, whereas no increase in IL-8 was detected in supernatants of identically treated HUVEC cultures. Histamine or thrombin treatment also caused IL-8–containing granules to rapidly disappear from HIMEC. In HUVEC, IL-8–containing granules were inducible by treatment with recombinant human IL-1β for 24 h; additional histamine treatment doubled IL-8 secretion from HUVEC in the same rapid manner observed for mucosal EC. These data suggested that IL-8 prestored in microvascular endothelial cells may provide a rapid pathway for specific activation of neutrophil adhesion at sites of acute inflammation.

Key Words: chemokine • inflammation • leukocyte adhesion • neutrophil recruitment • secretion

Address correspondence to Guttorm Haraldsen at his current address, Veterans Administration Medical Center (154B), Bldg. 101, Rm. C4-101, 3801 Miranda Ave., Palo Alto, CA 94304. Phone: 650-493-5000 ext. 63133; Fax: 650-858-3986; E-mail: guttormh{at}cmgm.stanford.edu


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