EXPRESSION OF FUNCTIONAL TRK PROTOONCOGENE IN HUMAN MONOCYTES

There is increasing evidence that neurotrophins, including nerve growt h factor (NGF), exert specific effects on cells of the immune system i n addition to their neurotrophic actions. This report shows that human monocytes express the trk protooncogene, encoding the signal-transduc ing receptor unit for NGF. This receptor is functional, since interact ion of NGF with monocytes triggered a respiratory burst, the major com ponent of monocyte cytotoxic activity. During in vitro differentiation of human blood monocytes to macrophages trk expression decreased, sug gesting a maturation-dependent trk regulation. Treatment of monocytes with Staphylococcus aureus Cowan 1, a potent activator of monocytes, s timulated trk mRNA synthesis in a time-dependent way, implying a modul atory role for NGF in immune functions. The finding that dibutyryl cAM P elicited a time-dependent trk induction in monocytes as well as in p horbol ester-differentiated promonocytic U937 cells indicates that ade nylate cyclase is involved in monocytic trk regulation. These results suggest that NGF, in addition to its neurotrophic function, is an immu noregulatory cytokine acting on monocytes.