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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 leukaemias8,9, 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 haemocytes13,14. 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.

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Shipp, M., Stefano, G., D'Adamio, L. et al. Downregulation of enkephalin-mediated inflammatory responses by CDl0/neutral endopeptidase 24.11. Nature 347, 394–396 (1990). https://doi.org/10.1038/347394a0

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