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Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-05-1500.
Submitted May 12, 2003
Accepted September 9, 2003
CD44-hyaluronic acid interactions mediate shear-resistant binding of lymphocytes to dermal endothelium in acute cutaneous GVHD
Mirjana Milinkovic, Joseph H Antin, Charles A Hergrueter, Charles B Underhill, and Robert Sackstein*
Department of Dermatology, Harvard Skin Disease Research Center, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
Division of Plastic Surgery, Brigham and Women's Hospital, Boston, MA, USA
Department of Oncology, School of Medicine, Georgetown University, Washington, DC, USA
* Corresponding author; email: rsackstein{at}rics.bwh.harvard.edu.
For circulating lymphocytes to migrate to inflammatory sites, they must first adhere to target tissue endothelium with sufficient strength to overcome the shear forces of blood flow. We previously reported that dermal papillary vessels in acute graft-versus-host disease (aGVHD) support shear-resistant lymphocyte adherence. We now identify the relevant adhesion molecule(s) directing this binding, showing that interactions between lymphocyte CD44 and hyaluronic acid (HA) expressed on dermal vessels in aGVHD alone confer this shear-resistant attachment. Native HA deposits on vascular endothelium support lymphocyte adherence whereas HA immobilized on plastic does not. HA expressed at dermal endothelium in aGVHD is thus specialized to support lymphocyte adherence under flow conditions, and CD44-HA interactions may contribute to lymphocytotropism to skin in aGVHD.
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