Lactoferrin Stimulates the Mitogen-Activated Protein Kinase in the Human Lymphoblastic T Jurkat Cell Line

Abstract

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 factor^6,7,12,17 and of interleukin⁹ synthesis, activation of NK cell activity¹³, inhibition of metastasis² and maturation of T- and B-cells^15,16. 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.