Cross-linking of LFA-1 induces secretion of macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta with consequent directed migration of activated lymphocytes

Cross-linking of LFA-1 induces an active locomotory phenotype in T cells. I n this study we demonstrate that cross-linking of LFA-1 using a monoclonal antibody results in the secretion of MIP-1 alpha and MIP-1 beta. Similar re sults were seen with anti-CD44 but not with anti-transferrin receptor or an ti-MHC class 1. We examined the ability of activated lymphocytes to migrate onto a substrate consisting of large protein G-Sepharose beads coated with anti-LFA-1 and anti-CD44. In this system a signal is provided by cells at the point of contact with the beads. Cells migrated to cover the bead surfa ce within 24 h. This contact was shown to be inhibited by the introduction of neutralizing antibodies to MIP-1 alpha and MIP-1 beta. Hence cross-linki ng of LFA-1 or CD44 induce chemokine secretion which may be of relevance in directional migration of lymphocytes.