Downregulation of enkephalin-mediated inflammatory responses by CDl0/neutral endopeptidase 24.11

Abstract

THE antigen CD10 (common acute lymphoblastic leukaemia antigen), which is the zinc metalloprotease, neutral endopeptidase 24.11 (also known as NEP or 'enkephalinase')^1–7, is expressed by acute lymphoblastic leukaemias^8,9, normal lymphoid progenitors¹⁰, mature polymorphonuclear leukocytes¹¹ and certain non-haematopoietic cells¹². CD10/NEP hydrolyses several naturally occurring peptides, including the endogenous opioid pentapeptides Met- and Leu-enkephalin⁶. In invertebrate organisms such as the mollusc Mytilus edulis, Met-enkephalin triggers inflammatory responses by inducing morphological changes, directed migration and aggregation of haemocytes^13,14. We report here that a structure related to CD10/NEP is expressed by M. edulis haemocytes and that abrogation of CD10/NEP enzymatic activity reduces the amount of Met-enkephalin required for haemocyte activation by five orders of magnitude. Similar results are obtained with CD10⁺ human polymorphonuclear leukocytes, indicating that CD10/NEP related structures regulate enkephalin-mediated inflammatory responses in organisms whose ancestors diverged ~500 million years ago¹⁵.