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on T Cell Rolling and Tight Adhesion to Monolayers of Activated Endothelial Cells1
Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717
Immobilized stromal cell-derived factor-1
(SDF-1) has been
shown to induce tight adhesion of T cells to purified ICAM-1 in assays
done under flow conditions. In this study, we show that soluble
SDF-1 induced a rapid (within 20 s) cessation of rolling and
tight adhesion of >90% of the rolling T cells on monolayers of
activated endothelial cells under similar flow. Within 4 min, the T
cells had either started to migrate between the endothelial cells or
re-entered the rolling and circulating lymphocyte pool. This
deadherence of the firmly bound cells, with either ensuing
transmigration or continued rolling, was most likely due to
desensitization of lymphocytes to the continuously present SDF-1.
The released rolling lymphocytes could still respond to other
activating signals by a second round of tight adhesion. Pretreating the
lymphocytes with pertussis toxin almost completely blocked the effect
of the chemokine, confirming that the induction of firm adhesion was
due to the function of the chemokine on the lymphocytes and not the
endothelial cells. Pretreating the endothelium with SDF-1 did not
lead to firm adhesion of subsequently added lymphocytes, also
indicating that the effect was due to soluble, not endothelially bound,
chemokine. Blocking experiments showed that the same molecules mediated
rolling before and after SDF-1-induced tight adhesion. This is the
first study to demonstrate the effect of soluble SDF-1 on T cell
rolling on an endothelial cell monolayer. The data broaden our
understanding of the stimulatory factors directing the firm adhesion
and ensuing transmigration of leukocytes into tissues through activated
endothelium.
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