Downregulation of enkephalin-mediated inflammatory responses by CD10/neutral endopeptidase 24.11.
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.
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, Massachusetts.
M A
MA
Shipp
G B
GB
Stefano
L
L
D'Adamio
S N
SN
Switzer
F D
FD
Howard
J
J
Sinisterra
B
B
Scharrer
E L
EL
Reinherz
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D049872:Bivalvia / Q000201:enzymology*; D015536:Down-Regulation; D004744:Enkephalin, Methionine / Q000378:metabolism / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology; D006434:Hemocytes / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008213:Lymphocyte Activation; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D013373:Substance P / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D006020:Glycopeptides; D013373:Substance P; D004744:Enkephalin, Methionine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015260:Neprilysin; C008890:phosphoramidon