INSERM Unité 575, IFR37 "Physiopathologie du Système Nerveux," Strasbourg, France
Laboratoire de Spectrometrie de Masse Bio-Organique, Universite Louis Pasteur, CNRS UMR 7509, ECPM, Strasbourg, France
Address for correspondence: M.H. Metz-Boutigue, INSERM Unité 575, IFR37 "Physiopathologie du Système Nerveux," 5 rue Blaise Pascal 67084, Strasbourg, France. Voice: 33-3-88-45-66-09; fax: 33-3-88-60-08-06.
metz{at}neurochem.u-strasbg.fr
Ann. N.Y. Acad. Sci. 992: 168-178 (2003).
The secretory granules from adrenal medullary chromaffin cells
contain a complex mixture of low-molecular mass constituents
such as catecholamines, ascorbate, nucleotides, calcium, peptides,
and several high-molecular mass water-soluble proteins including
chromogranins and proenkephalin-A. These proteins are sequestered
into secretory granules in which processing yields a large variety
of peptides. These fragments are released into the extracellular
space upon cell stimulation and are recovered in blood, lymph,
cerebrospinal fluid, and synovial fluid. Some of them have biological
activity on cells in an autocrine, paracrine, or endocrine fashion.
In addition, we have shown that peptides with antimicrobial
activity are present with the secretory chromaffin granules
and demonstrated that they are released from stimulated chromaffin
cells. We have shown that posttranslational modifications modulate
the antimicrobial activities. For some peptides, using confocal
laser microscopy, we have examined the interaction of the rhodaminated
peptides with biological membranes. In addition, we have shown
that chromofungin, the antifungal peptide corresponding to chromogranin
A
47-66, can bind calmodulin in the presence of calcium and induce
inhibition of calcineurin, a calmodulin-dependent enzyme. Because
these antibacterial peptides are colocalized with catecholamines,
they may be activated during stress, playing a role as a first
protective barrier against bacterial infection, and thus act
as factors of the innate immunity shortly after infection and
before the induction and mobilization of an adaptative immune
system.
