CD44 and its ligand hyaluronate mediate rolling under physiologic flow: a novel lymphocyte-endothelial cell primary adhesion pathway.
The extravasation of leukocytes from the blood into tissues occurs as a multistep process: an initial transient interaction ("rolling"), generally thought to be mediated by the selectin family of adhesion molecules, followed by firm adhesion, usually mediated by integrins. Using a parallel plate flow chamber designed to approximate physiologic flow in postcapillary venules, we have characterized a rolling interaction between lymphoid cells and adherent primary and cultured endothelial cells that is not selectin mediated. Studies using blocking monoclonal antibodies indicate that this novel interaction is mediated by CD44. Abrogation of the rolling interaction could be specifically achieved using both soluble hyaluronate (HA) and treatment of the adherent cells with HA-reactive substances, indicating that HA is the ligand supporting this rolling interaction. Some B and T cell lines, as well as normal lymphocytes, either constitutively exhibit rolling or can be induced to do so by phorbol ester or in vivo antigen activation. These studies indicate that CD44 and its principal ligand hyaluronate represent another receptor/carbohydrate ligand pair mediating a novel activation-dependent pathway of lymphocyte/endothelial cell adhesion.
DeGrendele
H C
HC
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, 75235-9072, USA.
Estess
P
P
Picker
L J
LJ
Siegelman
M H
MH
D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D002469:Cell Separation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000502:physiology*; D006820:Hyaluronic Acid / Q000502:physiology*; D007700:Kinetics; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid