TY - JOUR
T1 - CD44 and its ligand hyaluronate mediate rolling under physiologic flow
T2 - A novel lymphocyte-endothelial cell primary adhesion pathway
AU - DeGrendele, Heather C.
AU - Estess, Pila
AU - Picker, Louis J.
AU - Siegelman, Mark H.
PY - 1996/3/1
Y1 - 1996/3/1
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.183.3.1119
DO - 10.1084/jem.183.3.1119
M3 - Article
C2 - 8642254
AN - SCOPUS:0029966274
SN - 0022-1007
VL - 183
SP - 1119
EP - 1130
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 3
ER -