Letter
to the editor:
Immune cells express endocrine markers.
Michel Salzet
Received:
January 13, 2002
Laboratoire de Neuroimmunologie des Annélides, UMR
CNRS 8017, SN3, IFR 17 INSERM, Université des Sciences
et Technologies de Lille, 59655 Villeneuve d'Ascq, France.
Key
words:
Endocrinology, Neuroimmunity, Immunity
ABSTRACT:
Evidence are now given that immune cells expressed endocrine
markers like neuropeptides, biogenic amine, neuropeptide processing
enzymes, regulated secretion pathway. In clear, immune cells
expressed like the nervous system an endocrine phenotype. This
give the following question: what can we now consider as immune
or endocrine?
As suggested by Kvetnoy and colleagues (1) in the letter to
NEL editor entitled "Claude Bernard was right: hormones
may be produced by " non-endocrine " cells",
Claude Bernard was the first in 1855 to suppose that not only
endocrine glands but many organs in the organism have the ability
for "internal secretion" (2). The evidences that identical
biogenic amines and peptides hormones are found in neurones
and in amine precursor and uptake decarboxylation (APUD) cells
located in different organs firstly confirmed his visions of
the endocrinology (2). The existence of a diffuse neuroendocrine
system (DNES) concept was born (2). Recently, Weigent and Blalock
demonstrated that communication and reciprocal regulation between
the nervous, endocrine and immune systems are essential for
the stability of the organism, these three systems use the same
signalling molecules. (3) Among others, cytokines, hormones
and neuropeptides have been identified as messengers mediating
the communication between the three systems (4-8). Moreover,
in the last few years various animal models have served to study
neuroimmune mechanisms confirming the view of communication
between the neuroendocrine and immune systems via neuropeptide
signalling and through specific receptors (6-8).
Immune
cells are able to synthesise neuropeptides acting as signalling
molecules but also in organism defence (8-14). Peptides with
antibacterial properties have been shown to be derived from
neuropeptide precursors such as proenkephalin and chromogranin
B (8-14). The role of neuropeptide precursors in immunity, through
the release of antibacterial peptides, is an entirely novel
concept. The biosynthetic pathway that leads to the production
of biologically active neuropeptides begins with the synthesis
of large inactive precursor proteins which are cleaved at specific
paired or single basic residues within the Golgi secretory pathway
(15). It is a family of subtilase-like pro-protein convertases
(SPCs) (15) that is largely responsible for these processing
events that activate precursor proteins into neuropeptides.
The SPCs have been extensively studied in both neural and endocrine
systems. However, much less is known concerning their expression,
regulation and role within the immune system at the basal level
(15, 16) or their function during microbial challenge (4). We
recently demonstrate that SPC functions are important since
differential expression of SPCs and the resulting cleavage patterns
determine the nature and biological activity of the peptide
products. Thus, depending on the pattern of SPC expression,
a single protein precursor can give rise to different peptides
with diverse biological activities like antimicrobial substances
(secretolytin, enkelytin/peptide B, dermaseptins (9-13, 17)
or chemoattractant factors (Methionine-enkephalin) (7, 8).
Finally,
the important point is the presence of at least four different
types of granules formed during maturation of neutrophil granulocytes
in the bone marrow (18). Recent data support the concept that
the (lysosomal type) azurophil granules are secreted through
the endosomal pathway (19). Taken together, these data suggest
that regulated exocytosis from neutrophil granulocytes belongs
to the general mechanism of secretion.
Considering
all the above data, the aim of this letter is to point out that
some revisions of the fundamental postulates of classical endocrinology
need to be now undertaken.
Acknowledgements
The
Centre National de la Recherche Scientifique, the MNERT supported
this work.
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