LACTOFERRIN STIMULATES THE MITOGEN-ACTIVATED PROTEIN KINASE IN THE HUMAN LYMPHOBLASTIC T JURKAT CELL LINE

Lactoferrin11 (also called lactotransferrin) has been shown to be involved in numerous inflammatory and immune response functions such as regulation of granulocyte monocyte colony stimulating factor6,7,12,17 and of interleukin9 synthesis, activation of NK cell activity13, inhibition of metastasis2 and maturation of T- and B-cells15,16. Recently, it has also been demonstrated the activation of a nuclear reporter gene harbouring the spe-ci fic DNA sequence that lactoferrin recognizes8. Therefore, lactoferrin could be considered as a transcriptional factor1. It requires that lactoferrin is internalized and imported into the nucleus of target cells where it acts as a transcriptional factor1. However, there is no evidence that cell-surface lactoferrin receptors can transport lactoferrin either directly or via a new trafficking pathway to the nucleus. In order to investigate how lactoferrin affects the immune system, we have developed an experimental model using the human lymphoblastic T Jurkat cell line which upon lactoferrin treatment slowly undergoes a maturation process5. Jurkat cells express the lactoferrin receptor10 at the cell surface in coated-pit like domains, associated into clusters, and in different subsets of intracellular vesicles3 . Therefore, we have investigated the first intracellular events following the binding of lactoferrin to lymphocytes: internalization process of lactoferrin and activation of a transduction pathway.