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Some aspects of IL‐8 pathophysiology III: chemokine interaction with endothelial cells
Author(s) -
Rot Antal,
Hub Elin,
Middleton James,
Pons Françoise,
Rabeck Christa,
Thierer Kamillo,
Wintle Jonathan,
Wolff Barbara,
Zsak Marion,
Dukor Peter
Publication year - 1996
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.59.1.39
Subject(s) - chemokine , biology , microbiology and biotechnology , umbilical vein , endothelium , endothelial stem cell , monocyte , in vitro , secretion , interleukin 8 , immunology , chemotaxis , inflammation , receptor , biochemistry , endocrinology
Abstract Chemolrines have been convincingly implicated in driving leukocyte emigration in different inflammatory reactions. However, the cellular and molecular mechanisms of chemokine involvement in leukocyte emigration are not yet clear. We and others suggested that leukocyte adhesion to the endothelium and transmigration are induced by chemokines immobilised on the endothelial cell surface. This would require the presence of specific chemokine binding sites in this microanatomical location. Using an in situ binding assay we demonstrated the presence of binding sites for interleukin‐8 (IL‐8) and RANTES, but not monocyte inflammatory protein‐1α on the endothelium of postcapillary venules and small veins in human skin. In contrast, venules and veins in various anatomical locations showed dramatically differing IL‐8 binding patterns. The subcellular distribution of IL‐8 in the venular endothelial cells following its in vivo and ex vivo injections was studied by use of electron microscopy. Our results suggest that IL‐8 was internalized by the endothelial cells, transported transcellularly via plasmalemmal vesicles, and released onto the luminal surface where it appeared located preferentially on tips of membrane protrusions. We were unable to study the endothelial IL‐8 binding or transport in vitro because all the in vitro propagated endothelial cell lines and primary endothelial cells tested lacked IL‐8 binding sites. This includes human umbilical vein endothelial cells (HUVECs), which also did not bind IL‐8 in situ. However, HUVECs provided a satisfactory in vitro system to study the secretion of IL‐8 by the endothelial cells. Two possible alternative pathways were described: secretion directly from the Golgi apparatus or following storage in Weibel‐Palade bodies.