CD44 cross-linking induces protein kinase C-regulated migration of human T lymphocytes

Abstract

The cell surface receptor CD44 is widely implicated in leukocyte migration to inflammatory sites. In this study, the responses of human T cells following cross-linking of CD44 were examined. We demonstrate that engagement of CD44 using immobilized mAbs or hyaluronan-enriched extracellular matrix lattices induces active migration in T lymphocytes accompanied by cycles of cytoskeletal rearrangement and cell polarization. We have investigated the functional impact and subcellular localization of protein kinase C (PKC) isoenzymes, β and δ, previously shown by our group to be involved in active T cell locomotion induced by leukocyte function-associated antigen-1 (LFA-1) integrin receptors. PKCβ was associated with the centrosome and the microtubule-rich tail of the polarized cell and PKCδ was predominantly located about the region of the microtubule organizing center. A selective pharmacological inhibitor of classical PKC isoforms, Gö6976, suppressed lymphocyte polarization and migration following CD44 ligation. Selective targeting of PKCδ using the pharmacological inhibitor rottlerin or a pseudosubstrate-blocking peptide reduced CD44-activated cell migration but did not completely ablate it. Our data demonstrate that ligation of CD44 induces phenotypic changes, cytoskeletal rearrangements and redistribution of PKC isoforms β and δ, resulting in cell migration, as previously described for the cell surface receptor, LFA-1. This suggests potential convergence of intracellular signaling pathways induced via CD44 and LFA-1 integrin. © The Japanese Society for Immunology 2005. All rights reserved.