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Blood, Vol. 93 No. 9 (May 1), 1999:
pp. 2791-2797
Mast Cell Migratory Response to Interleukin-8 Is Mediated Through
Interaction With Chemokine Receptor CXCR2/Interleukin-8RB
Gunnar Nilsson,
Judy A. Mikovits,
Dean D. Metcalfe, and
Dennis D. Taub
From the Department of Genetics and Pathology, Uppsala University,
Uppsala, Sweden; Science Applications International
Corporation-Frederick, National Cancer Institute-Frederick Cancer
Research and Development Program, Frederick, MD; Laboratory of Allergic
Diseases, National Institute of Allergy and Infectious Diseases,
National Institutes of Health (NIH), Bethesda, MD; and Clinical
Immunology Section, Laboratory of Immunology, National Institute on
Aging, NIH, Baltimore, MD.
To explore the role of chemokines in mast cell chemotaxis and
accumulation at sites of inflammation, we first investigated the
response of human mast cells to 18 different chemokines by induction of
intracellular calcium mobilization in the human mast cell line, HMC-1.
Only a subgroup of CXC chemokines defined by the conserved sequence
motif glutamic acid-leucine-arginine (ELR) tripeptide motif, which
included interleukin-8 (IL-8), growth-regulated oncogene  (GRO),
neutrophil-activating peptide-2 (NAP-2), and epithelial cell-derived
neutrophil activating peptide-78 (ENA-78), induced calcium flux in the
cells. These observations suggested that the receptor CXCR2 (IL-8RB)
should be expressed on the surface of these cells. Using the RNAse
protection assay, CXCR2 mRNA, but not CXCR1 (IL-8RA) mRNA expression
was detected in HMC-1 cells. Flow cytometry analysis documented the
surface expression of CXCR2. A binding analysis performed with
125I-IL-8 determined that there were approximately 3,600 high affinity IL-8 binding sites per HMC-1 cell, with a calculated
kd of 1.2 to 2 nmol/L. The activity of this receptor was
further explored using IL-8, which was found to induce dose-dependent
chemotactic and haptotactic responses in both HMC-1 cells and in vitro
cultured human cord blood-derived mast cells. These results show the
expression of functional CXCR2 receptors on the surface of human mast
cells, which may play an important role in mast cell recruitment during the genesis of an inflammatory response.
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