The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/2/627/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 4, February 15, 1999 627-636

Articles

Interaction of Dendritic Cells with Skin Endothelium: A New Perspective on Immunosurveillance

Caroline Robert*, Robert C. Fuhlbrigge*, J. David Kieffer*, Seyoum Ayehunie{ddagger}, Richard O. Hynes§, Guiying Cheng||, Stephan Grabbe*, Ulrich H. von Andrian||, and Thomas S. Kupper*

From the * Harvard Skin Disease Research Center, Division of Dermatology, Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, Massachusetts 02115; {ddagger} 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

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.

Key Words: inflammation • immunosurveillance • selectins • rolling • extravasation

Address correspondence to Thomas S. Kupper, Harvard Skin Disease Research Center, Division of Dermatology, Department of Medicine, Brigham and Women's Hospital, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02115. Phone: 617-525-5550; Fax: 617-525-5571; E-mail: tskupper{at}rics.bwh.harvard.edu

Abbreviations used: CLA, cutaneous lymphocyte-associated antigen; DC, dendritic cell; PSGL-1, P-selectin glycoprotein ligand 1; VCAM-1, vascular cell adhesion molecule 1; VLA-4, very late antigen 4.


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