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Blood, 15 July 2002, Vol. 100, No. 2, pp. 553-559
IMMUNOBIOLOGY
Presence of chromogranin-derived antimicrobial peptides in
plasma during coronary artery bypass surgery and evidence of an
immune origin of these peptides
Aurélie Tasiemski,
Hamida Hammad,
Franck Vandenbulcke,
Christophe Breton,
Thomas J. Bilfinger,
Joel Pestel, and
Michel Salzet
From the Laboratoire de Neuroimmunologie des
Annélides, Université des Sciences et Technologies de
Lille, Villeneuve d'ascq, France; Unite INSERM U-416, Institut Pasteur
de Lille, France; and the Cardiac Research Program, Department of
Surgery, Health Sciences Center, State University of New York, Stony
Brook.
Chromogranin A (CGA) and chromogranin B (CGB) are acidic proteins
stored in secretory organelles of endocrine cells and neurons. In
addition to their roles as helper proteins in the packaging of
peptides, they may serve as prohormones to generate biologically active
peptides such as vasostatin-1 and secretolytin. These molecules derived
from CGA and CGB, respectively, possess antimicrobial properties. The
present study demonstrates that plasmatic levels of both vasostatin-1
and secretolytin increase during surgery in patients undergoing
cardiopulmonary bypass (CPB). Vasostatin-1 and secretolytin, initially
present in plasma at low levels, are released just after skin incision.
Consequently, they can be added to enkelytin, an antibacterial peptide
derived from proenkephalin A, for the panoply of components acting as a
first protective barrier against hypothetical invasion of pathogens,
which may occur during surgery. CGA and CGB, more commonly viewed as
markers for endocrine and neuronal cells, were also found to have an
immune origin. RNA messengers coding for CGB were amplified by reverse transcription-polymerase chain reaction in human monocytes, and immunocytochemical analysis by confocal microscopy revealed the presence of CGA or CGB or both in monocytes and neutrophils. A combination of techniques including confocal microscopic analysis, mass
spectrometry measurement, and antibacterial tests allowed for the
identification of the positive role of interleukin 6 (IL-6) in the
secretolytin release from monocytes in vitro. Because IL-6 release is
known to be strongly enhanced during CPB, we suggest a possible
relationship between IL-6 and the increased level of secretolytin in
patients undergoing CPB.
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