Pachymodulin, a New Functional
Formyl Peptide Receptor
2 Peptidic Ligand Isolated from Frog Skin Has Janus-like Immunomodulatory
Capacities
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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 <i>Pachymedusa dacnicolor,</i> which we named pachymodulin. In
vitro, pachymodulin promotes the migration of leukocytes through the
binding and activation of the human and mouse <i>N</i>-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