CD44 AND ITS LIGAND HYALURONATE MEDIATE ROLLING UNDER PHYSIOLOGICAL 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''), g enerally thought to be mediated by the selectin family of adhesion mol ecules, followed by firm adhesion, usually mediated by integrins. Usin g a parallel plate now chamber designed to approximate physiologic now 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 u sing both soluble hyaluronate (HA) and treatment of the adherent cells with HA-reactive substances, indicating that HA is the ligand support ing this rolling interaction. Some B and T cell lines, as well as norm al lymphocytes, either constitutively exhibit rolling or can be induce d to do so by phorbol ester or in vivo antigen activation. These studi es indicate that CD44 and its principal ligand hyaluronate represent a nother receptor/carbohydrate ligand pair mediating a novel activation- dependent pathway of lymphocyte/endothelial cell adhesion.