title: Pachymodulin, a new functional formyl peptide receptor 2 peptidic ligand isolated from frog skin has Janus-like immunomodulatory capacities.
abstract: Recruitment of leukocytes is essential to fight infections or to heal injuries; however, excessive and/or prolonged responses favor the development of major inflammatory pathologies, such as cardiovascular or neurodegenerative diseases. Thus, it is of great interest to seek novel compounds that can regulate leukocyte recruitment depending on the degree of inflammation. We have isolated and characterized, by different chromatographic techniques, mass spectrometry, and Edman sequencing, a new hexapeptide (SSLSKL) from the Mexican frog Pachymedusa dacnicolor, which we named pachymodulin. In vitro, pachymodulin promotes the migration of leukocytes through the binding and activation of the human and mouse N-formyl peptide receptor 2 (huFPR2). In vivo, it exhibits opposite biological activities: under homeostatic conditions, pachymodulin induces the recruitment of leukocytes, whereas under inflammatory conditions, it inhibits this process. Therefore, pachymodulin represents an interesting template in the quest to design new immunomodulatory drugs in the therapy of immune-related diseases.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM , 4 place Jussieu, 75005 Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Lacombe
authors.forename: Christophe
authors.initials: C
authors.lastname: Piesse
authors.forename: Sandrine
authors.initials: S
authors.lastname: Sagan
authors.forename: Christophe
authors.initials: C
authors.lastname: Combadière
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Rosenstein
authors.forename: Constance
authors.initials: C
authors.lastname: Auvynet
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001001:Anura; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy; D007962:Leukocytes / Q000187:drug effects; D008024:Ligands; D051379:Mice; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012867:Skin / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C105101:FPR2 protein, human; D007155:Immunologic Factors; D008024:Ligands; D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C481578:formyl peptide receptor 2, mouse; C000596769:seryl-seryl-leucyl-seryl-lysyl-leucine