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J. Exp. Med.,
Volume 189, Number 4, February 15, 1999 627-636
By
From the * Harvard Skin Disease Research Center, Division of Dermatology, Brigham and Women's
Hospital, Harvard Institutes of Medicine, Boston, Massachusetts 02115; The goal of this study was to determine the mechanisms by which dendritic cells (DCs) in
blood could interact with endothelium, a prerequisite to extravasation into tissues. Our results
indicate that DCs express both HECA-452-reactive and nonreactive isoforms of P-selectin
glycoprotein ligand 1 (PSGL-1) and can tether and roll efficiently on E- and P-selectin under
flow conditions in vitro. Freshly isolated blood DCs were further observed to roll continuously
along noninflamed murine dermal endothelium in vivo. This interaction is strictly dependent
on endothelial selectins, as shown by experiments with blocking antibodies and with E- and P-selectin-deficient mice. We hypothesize that DCs in blood are constitutively poised at the
interface of blood and skin, ready to extravasate upon induction of inflammation, and we
showed that cutaneous inflammation results in a rapid recruitment of DCs from the blood to
tissues. We propose that this is an important and previously unappreciated element of immunosurveillance.
MatTek Corporation,
Ashland, Massachusetts 01721; the § Center for Cancer Research, Department of Biology, Howard
Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 01239;
and the Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115
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