PMID- 15044249 OWN - NLM STAT- MEDLINE DCOM- 20040817 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 104 IP - 2 DP - 2004 Jul 15 TI - Rapid chemokine secretion from endothelial cells originates from 2 distinct compartments. PG - 314-20 AB - The neutrophil-attracting chemokine interleukin 8 (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 growth-related oncogene alpha (GROalpha), monocyte chemoattractant protein-1 (MCP-1), eotaxin-3, interferon-gamma-inducible protein 10 (IP-10), and regulated on activation, normal T-cell expressed and secreted (RANTES). While eotaxin-3, GROalpha, 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 3 former chemokines, only eotaxin-3 was stored in WPBs. GROalpha 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. FAU - Oynebraten, Inger AU - Oynebraten I AD - LIIPAT, Institute of Pathology, Rikshospitalet, N-0027 Oslo, Norway. inger.oynebraten@labmed.uio.no FAU - Bakke, Oddmund AU - Bakke O FAU - Brandtzaeg, Per AU - Brandtzaeg P FAU - Johansen, Finn-Eirik AU - Johansen FE FAU - Haraldsen, Guttorm AU - Haraldsen G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20040325 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (CCL26 protein, human) RN - 0 (CXCL1 protein, human) RN - 0 (Carcinogens) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL26) RN - 0 (Chemokine CCL5) RN - 0 (Chemokine CXCL1) RN - 0 (Chemokine CXCL10) RN - 0 (Chemokines) RN - 0 (Chemokines, CC) RN - 0 (Chemokines, CXC) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Interleukin-8) RN - 0 (von Willebrand Factor) RN - 820484N8I3 (Histamine) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Carcinogens/pharmacology MH - Cell Compartmentation/*physiology MH - Cells, Cultured MH - Chemokine CCL2/metabolism MH - Chemokine CCL26 MH - Chemokine CCL5/metabolism MH - Chemokine CXCL1 MH - Chemokine CXCL10/metabolism MH - Chemokines/*metabolism MH - Chemokines, CC/metabolism MH - Chemokines, CXC/metabolism MH - Cytoplasm/metabolism MH - Endothelium, Vascular/cytology/drug effects/*metabolism MH - Histamine/pharmacology MH - Humans MH - Intercellular Signaling Peptides and Proteins/metabolism MH - Interleukin-8/metabolism MH - Secretory Vesicles/drug effects/metabolism MH - Tetradecanoylphorbol Acetate/pharmacology MH - Umbilical Veins/cytology MH - Weibel-Palade Bodies/metabolism MH - von Willebrand Factor/metabolism EDAT- 2004/03/27 05:00 MHDA- 2004/08/18 05:00 CRDT- 2004/03/27 05:00 PHST- 2004/03/27 05:00 [pubmed] PHST- 2004/08/18 05:00 [medline] PHST- 2004/03/27 05:00 [entrez] AID - S0006-4971(20)55122-7 [pii] AID - 10.1182/blood-2003-08-2891 [doi] PST - ppublish SO - Blood. 2004 Jul 15;104(2):314-20. doi: 10.1182/blood-2003-08-2891. Epub 2004 Mar 25.