EXPRESSION OF FUNCTIONAL TRK PROTOONCOGENE IN HUMAN MONOCYTES

There is increasing evidence that neurotrophins, including nerve growth factor (NGF), exert specific effects on cells of the immune system in addition to their neurotrophic actions. This report shows that human monocytes express the trk protooncogene, encoding the signal-transducing receptor unit for NGF. This receptor is functional, since interaction of NGF with monocytes triggered a respiratory burst, the major component of monocyte cytotoxic activity. During in vitro differentiation of human blood monocytes to macrophages trk expression decreased, suggesting a maturation-dependent trk regulation. Treatment of monocytes with Staphylococcus aureus Cowan 1, a potent activator of monocytes, stimulated trk mRNA synthesis in a time-dependent way, implying a modulatory role for NGF in immune functions. The finding that dibutyryl cAMP elicited a time-dependent trk induction in monocytes as well as in phorbol ester-differentiated promonocytic U937 cells indicates that adenylate cyclase is involved in monocytic trk regulation. These results suggest that NGF, in addition to its neurotrophic function, is an immunoregulatory cytokine acting on monocytes.