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

Margaret A. Shipp, George B. Stefano, Luciano D'Adamio, Stephanie N. Switzer, Frank D. Howard, Juan Sinisterra, Berta Scharrer, Ellis L. Reinherz

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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.

Original languageEnglish (US)
Pages (from-to)394-396
Number of pages3
JournalNature
Volume347
Issue number6291
DOIs
Publication statusPublished - Jan 1 1990

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Shipp, M. A., Stefano, G. B., D'Adamio, L., Switzer, S. N., Howard, F. D., Sinisterra, J., ... Reinherz, E. L. (1990). Downregulation of enkephalin-mediated inflammatory responses by CDl0/neutral endopeptidase 24.11. Nature, 347(6291), 394-396. https://doi.org/10.1038/347394a0