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Blood, 15 July 2004, Vol. 104, No. 2, pp. 314-320.
Prepublished online as a Blood First Edition Paper on March 25, 2004; DOI 10.1182/blood-2003-08-2891.
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Submitted August 27, 2003
Accepted March 11, 2004
Rapid chemokine secretion from endothelial cells originates from two distinct compartments
Inger Oynebraten*, Oddmund Bakke, Per Brandtzaeg, Finn-Eirik Johansen, and Guttorm Haraldsen
Institute of Pathology, Rikshospitalet, Oslo, Norway
IBMB, University of Bergen, Bergen, Norway
* Corresponding author; email: inger.oynebraten{at}labmed.uio.no.
The neutrophil-attracting chemokine IL-8 is stored in the Weibel-Palade body (WPB) of endothelial cells (ECs) from which it can be rapidly released after exposure to the secretagogues histamine or thrombin. In this manner, IL-8 may enable rapid recruitment of leukocytes to inflammatory sites. To explore the possible storage of EC-derived chemokines that may attract other subsets of leukocytes, we examined the intracellular localization and secretagogue responsiveness of GRO , MCP-1, eotaxin-3, IP-10, and RANTES. While eotaxin-3, GRO and MCP-1 were rapidly released from ECs, the release of the T-cell attractors RANTES and IP-10 was not sensitive to the secretagogues. Moreover, of the three former chemokines, only eotaxin-3 was stored in WPBs. GRO and MCP-1 resided mainly in smaller vesicles compatible with sorting to a different, histamine-responsive compartment, which has been described in ECs although not reported to contain chemokines. In conclusion, we propose that rapid release of chemokines is restricted to those primarily recruiting leukocytes of the innate immune system, and that their storage in ECs is not restricted to the WPB compartment.
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