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Submitted on September 25, 2003
Accepted on November 12, 2003
-endorphin synthesis, processing and release from immunocytes in inflammatory pain
1 Klinik für Anaesthesiologie und operative Intensivmedizin, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, D-12200 Berlin, Germany; Institut für Anatomie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Königin-Luise-Stra
e 15, D-14195 Berlin, Germany
* To whom correspondence should be addressed. E-mail: Shaaban{at}zop-admin.ukbf.fu-berlin.de.
The opioid peptide -endorphin (END) as well as mRNA for its precursor pro-opiomelanocortin (POMC) are not only found in the pituitary gland but also within various types of immune cells infiltrating inflamed subcutaneous tissue. During stressful stimuli END is released and interacts with peripheral opioid receptors to inhibit pain. However, the subcellular pathways of POMC processing and END release have not yet been delineated in inflammatory cells. The aim of the present study was to examine the presence of POMC, carboxypeptidase E (CPE), the prohormone convertases 1 (PC1), and 2 (PC2), PC2 binding protein 7B2, and the release of END from inflammatory cells in rats. Using immunohistochemistry we detected END and POMC alone or colocalized with PC1, PC2, CPE, and 7B2 in macrophages/monocytes, granulocytes, and lymphocytes of the blood and within inflamed subcutaneous paw tissue. Immunoelectron microscopy revealed that END is localized within secretory granules packed in membranous structures in macrophages, monocytes, granulocytes, and lymphocytes. Finally, END is released by noradrenaline from immune cells in vitro. Taken together, our results indicate that immune cells express the entire machinery required for POMC processing into functionally active peptides such as END and are able to release these peptides from secretory granules.
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