BINDING OF HUMAN-LEUKOCYTES TO FIBRONECTIN IS AUGMENTED BY AN ANTI-CD44 MAB (TL-1) AND BLOCKED BY ANOTHER ANTI-CD44 MAB (HERMES-3) BUT NOT BY ANTI-VLA-4 VLA-5 MABS/

Fibronectin (FN) forms meshworks in extracellular spaces, and it plays an important role in cellular trafficking. Lymphoid cells are activat ed bq binding to FN of the VLA-4 and VLA-S receptors. CD44 also acts a s a receptor of FN, but the mechanism and physiologic regulation of th eir binding are poorly understood. We have developed an anti-CD44 mono clonal antibody (mAb) (TL-1) in which lymphoid cells are activated and form homotypic cell aggregation. In this study we found that the adhe sion of GEM, HSB2, and LAD lymphoid cells to FN was augmented by TL-1 treatment and was apparently blocked by another anti-CD44 mAb (Hermes- 3), but TL-1 Fab' fragments treatment did not induce FN-binding. A sim ilar phenomenon is reported in the binding of the CD44 molecule to HA. This augmentation was not inhibited by the CSI and RGD peptides of FN or by anti-VLA-4 and -VLA-5 mAbs; it was energy-dependent and associa ted with cytoplasmic actin filaments. Tl-1 treatment did not alter the cell surface expression of CD44 molecules. These findings above sugge sted that activated and/or altered sell surface distribution of CD44 m olecules via a conformational change augmented the avidity of its bind ing to FN, which may be similar to lymphocyte-hyaluronate and lymphocy te-endothelial cell binding. As the Hermes-3 binding site is also invo lved in the interaction between lymphocytes and endothelial cells, act ivation of lymphocytes via CD44 molecules may facilitate the binding o f lymphocytes to endothelial cells, extravasation, and migration to in flammatory sites rich in FN.