Lactoferrin upregulates the expression of CD4 antigen through the stimulation of the mitogen-activated protein kinase in the human lymphoblastic T Jurkat cell line

The main biological properties of lactoferrin are thought to concern inflam mation and immunomodulation processes, including maturation of immature B a nd T cells. Lactoferrin accelerates T-cell maturation by inducing the expre ssion of the CD4 surface marker. In this report, using the Jurkat T-cell li ne, Lye have shown that lactoferrin upregulates the expression of CD4 antig en through the activation of a transduction pathway. Using an antiphosphoty rosine antibody, lactoferrin was demonstrated to induce a cascade of phosph orylation of numerous proteins on their tyrosine residues. This tyrosine-ph osphorylation was transient, reaching maxima between 5 and 10 min. We also identified the mitogen-activated protein kinase (MAP kinase) which presente d an enhanced catalytic activity, reaching a maximum at 10 min of incubatio n with lactoferrin. Moreover, the use of inhibitors such as genistein and P D98059, tyrosine kinases and MAP kinase kinase (or MEK) inhibitors respecti vely, allowed us to correlate the activation of MAP kinase with the upregul ation of CD4 expression. Finally, using Lck-defective Jurkat cells, our res ults showed that the p56(lek) (Lck) kinase is necessary for MAP kinase acti vity and CD4 expression. This paper demonstrates that lactoferrin activates transduction pathway(s) in lymphoblastic T-cells, and that Lck and the Erk 2 isoform of MAP kinase are implicated in the upregulation of CD4, induced by lactoferrin in these cells. (C) 2000 Wiley-Liss. Inc.