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Departments of
*
Internal Medicine and
Periodontology, Osaka Dental University, Hanazono-cho, Hirakata-shi, Osaka, Japan;
Department of Microbiology, Kinki University School of Medicine, Ohno-Higashi, Osaka-Sayama, Osaka, Japan;
§
Department of Hematology and Oncology, Kyoto University Graduate School of Medicine, Shogoinn-Kawara-cho, Sakyo-ku, Kyoto, Japan; and
¶
Division of Cellular and Gene Therapies, Center for Biologics Evaluation Research, Food and Drug Administration, Bethesda, MD 20892
Leukocyte adhesion and trafficking at the endothelium requires both
cellular adhesion molecules and chemotactic factors. A newly identified
CX3C chemokine, fractalkine, expressed on activated
endothelial cells, plays an important role in leukocyte adhesion and
migration. We examined the functional effects of fractalkine on
ß1 and ß2 integrin-mediated adhesion using
a macrophage-like cell line, THP-1 cells. In this study, we report that
THP-1 cells express mRNA encoding a receptor for fractalkine,
CX3CR1, determined by Northern blotting. Scatchard analysis
using fractalkine-SEAP (secreted form of placental alkaline
phosphatase) chimeric proteins revealed that THP-1 cells express a
single class of CX3CR1 with a dissociation constant of 30
pM and a mean expression of 440 sites per cell. THP-1 cells efficiently
adhered, in a fractalkine-dependent manner, to full-length
of fractalkine immobilized onto plastic and to the membrane-bound form
of fractalkine expressed on ECV304 cells or TNF-
-activated HUVECs.
Moreover, soluble-fractalkine enhanced adhesion of THP-1 cells to
fibronectin and ICAM-1 in a dose-dependent manner. Pertussis toxin, an
inhibitor of Gi, inhibited the fractalkine-mediated
enhancement of THP-1 cell adhesion to fibronectin and ICAM-1. Finally,
we found that soluble-fractalkine also enhanced adhesion of freshly
separated monocytes to fibronectin and ICAM-1. These results indicate
that fractalkine may induce firm adhesion between monocytes and
endothelial cells not only through an intrinsic adhesion function
itself, but also through activation of integrin avidity for their
ligands.
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A. D. Lucas, N. Chadwick, B. F. Warren, D. P. Jewell, S. Gordon, F. Powrie, and D. R. Greaves The Transmembrane Form of the CX3CL1 Chemokine Fractalkine Is Expressed Predominantly by Epithelial Cells in Vivo Am. J. Pathol., March 1, 2001; 158(3): 855 - 866. [Abstract] [Full Text] [PDF]
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 D. H. McDermott, J. P.J. Halcox, W. H. Schenke, M. A. Waclawiw, M. N. Merrell, N. Epstein, A. A. Quyyumi, and P. M. Murphy Association Between Polymorphism in the Chemokine Receptor CX3CR1 and Coronary Vascular Endothelial Dysfunction and Atherosclerosis Circ. Res., August 31, 2001; 89(5): 401 - 407. [Abstract] [Full Text] [PDF]
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