Lactoferrin derived from neutrophils inhibits the mixed lymphocyte reaction

The effects of the products of phagocytosing neutrophils on lymphocyte transcriptional activity have been investigated using allogeneic mixed lymphocyte cultures (MLC). When MLCs are grown crowded in round- bottomed wells, uptake of tritiated uridine is inhibited by the presence of neutrophil products. Similarly, inhibitory activity is shown by purified lactoferrin. The inhibitory factor released by neutrophils is positively identified as lactoferrin, since its activity is lost in the presence of specific antibody. In addition, inhibitory activity is lost when lactoferrin is removed by a monoclonal antibody (MoAb) column and is recovered with lactoferrin from the column. The active form of lactoferrin carries iron and the apoprotein is inactive. MLCs crowded in round-bottomed wells take up considerably more uridine than when spread in flat-bottomed wells, and it is this enhanced transcriptional activity that is inhibited by neutrophil-derived lactoferrin. Enhanced uridine uptake by crowded cultures is due to factors that can be transferred in the supernatants to promote uridine uptake by spread cultures. Neutrophil lactoferrin inhibits both production and effect of the transferable factor(s).