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1
Departments of
*
Microbiology and Immunology,
Pathology, and
Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
Mature mast cells are generally considered to be less mobile cells
residing within tissue sites. However, mast cell numbers are known to
increase in the context of inflammation, and mast cells are recognized
to be important in regulating local neutrophil infiltration. CXC
chemokines may play a critical role in this process. In this study two
human mast cell-like lines, HMC-1 and KU812, and human cord
blood-derived primary cultured mast cells were employed to examine role
of stromal cell-derived factor-1 (SDF-1) in regulating mast cell
migration and mediator production. It was demonstrated that human mast
cells constitutively express mRNA and protein for CXCR4. Stimulation of
human mast cells with SDF-1, the only known ligand for CXCR4, induced a
significant increase in intracellular calcium levels. In vitro,
SDF-1
mediated dose-dependent migration of human cord blood-derived
mast cells and HMC-1 cells across HUVEC monolayers. Although SDF-1
did not induce mast cell degranulation, it selectively stimulated
production of the neutrophil chemoattractant IL-8 without affecting
TNF-, IL-1ß, IL-6, GM-CSF, IFN-
, or RANTES production,
providing further evidence of the selective modulation of mast cell
function by this chemokine. These findings provide a novel,
SDF-1-dependent mechanism for mast cell transendothelial migration and
functional regulation, which may have important implications for the
local regulation of mast cells in disease.
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