Proenkephalin A-derived peptides in invertebrate innate immune processes.
Lipopolysaccharides (LPS) injection into the coelomic fluid of the leech Theromyzon tessulatum stimulates release of proenkephalin A (PEA)-derived peptides as determined by immunoprecipitation and Western blot analyses. This release occurs in the first 15 min after LPS exposure and yields a 5.3-kDa peptide fragment corresponding to the C-terminal part of the precursor. This fragment is then cleaved to free an antibacterial peptide related to mammals arginine phenylalanine extended enkelytin: the peptide B. These PEA processing peptides were characterized using a combination of techniques including reversed-phase HPLC, microsequencing and mass spectrometry. The isolated invertebrate peptide B presents a high sequence homology with the bovine's and the same activity against Gram+bacteria. Titrations revealed the simultaneous appearance of Methionine-enkephalin (ME) and peptide B in invertebrates after stimulation by LPS (in a dose-dependent manner), surgical trauma or electrical stimulations to neural tissues of the mussel. Furthermore, peptide B processing in vitro yields Methionine-enkephalin arginine phenylalanine (MERF), which exhibits via the delta receptors, immunocyte excitatory properties, i.e., movement and conformational changes, but no antibacterial activity. We surmise that this unified response to the various stimuli is a survival strategy for organism by providing immediate antibacterial activity and immunocyte stimulation, thereby reducing any immune latency period needed for an adequate immune response.
Tasiemski
A
A
Laboratoire d'Endocrinologie des Annélides, UPRES-A CNRS 8017, SN3, Université des Sciences et Technologies de Lille, F-59655 Villeneuve d'Ascq Cédex, France.
Verger-Bocquet
M
M
Cadet
M
M
Goumon
Y
Y
Metz-Boutigue
M H
MH
Aunis
D
D
Stefano
G B
GB
Salzet
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D004597:Electroshock; D004745:Enkephalins / Q000737:chemistry / Q000378:metabolism*; D007150:Immunohistochemistry; D007700:Kinetics; D007865:Leeches / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D004745:Enkephalins; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D011498:Protein Precursors; C099820:enkelytin; C029992:proenkephalin