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'), is expressed by acute lymphoblastic leukaemias, normal lymphoid progenitors, mature polymorphonuclear leukocytes and certain nonhaematopoietic cells. CD10/NEP hydrolyses several naturally occurring peptides, including the endogenous opioid pentapeptides Met- and Leu-enkephalin. In invertebrate organisms such as the mollusc Mytilus edulis, Met-enkephalin triggers inflammatory responses by inducing morphological changes, directed migration and aggregation of haemocytes. 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 approximately 500 million years ago.

Neutral endopeptidase 24.11 in neutrophils modulates protective effects of natriuretic peptides against neutrophils-induced endothelial cytotoxity.

“…Neutral endopeptidase 24.11 (NEP), a membrane ectoenzyme, hydrolyses and inactivates a variety of peptides including ANP and BNP at the amino side of hydrophobic amino acids (11)(12)(13)(14)(15)(16)(17). NEP is widely distributed in the body and is abundant especially in the kidney (11), lung (12), brain (13), and neutrophils (14)(15)(16)(17). The gene of NEP has been cloned and its sequence is shown to be identical to that of a pre-␤ lymphocyte surface antigen (CD10), the common acute lymphoblastic leukemia antigen (CALLA) (18,19).…”

CD10/neutral endopeptidase 24.11 in developing human fetal lung. Patterns of expression and modulation of peptide-mediated proliferation.

“…This cell membrane-associated enzyme (CDlO/NEP)' hydrolyzes a number of naturally occurring peptides, including the endogenous opioid pentapeptides Met-and Leu-enkephalin, substance P, neurotensin, oxytocin, bradykinin, angiotensins 1 and 2, atrial natriuretic factor, endothelin and the chemotactic peptide, f MLP (2,(4)(5)(6). CDlO/NEP, which is expressed on early lymphoid progenitors, neutrophils, and a variety of nonhematopoietic cell types (5)(6)(7)(8), functions in multiple organ systems to downregulate induced responses to peptide hormones (9)(10)(11)(12)(13)(14)(15)(16). For instance, CD lO/NEP is expressed at high levels in the lung (17)(18)(19), where it modulates responses to tachykinins such as substance P that mediate neurogenic inflammation (9)(10)(11)(12)16).…”

Utility of CD10 in Distinguishing between Endometrial Stromal Sarcoma and Uterine Smooth Muscle Tumors: An Immunohistochemical Comparison of 34 Cases

“…CD10 functions as a cell surface enzyme that acts to reduce cellular response to peptide hormones by regulating local peptide concentration (17). Thus, many hormone-sensitive and peptidesensitive cells and their corresponding neoplasms express CD10 antigen (18 -21), including normal endometrial stroma and ESS (22)(23)(24).…”