Production of procalcitonin (PCT) in non-thyroidal tissue after LPS injection.
Procalcitonin (PCT) is one of the precursors in the synthesis of calcitonin in thyroidal C-cells and other neuroendocrine cells. PCT, among other calcitonin precursors, is elevated in the serum of many conditions associated with a systemic inflammatory response syndrome, even in the absence of the thyroid gland. The aim of our study was to identify PCT-producing extrathyroidal tissues in primate sepsis. In order to induce PCT production, we treated four olive baboons ( papio cynocephalus anubis) with the endotoxin lipopolysaccharide (LPS) from s. typhimurium. We found an increase in serum PCT 3 to 5 hours after LPS injection to levels of 0.2 ng/ml, attaining a peak above 4 ng/ml PCT at 10 hours. In contrast, the untreated baboon had no detectable circulating PCT in the serum. In one animal, additional LPS boosting after 24 hours did not increase serum PCT further. Soluble proteins were extracted from different organs, fractionated by C18 extraction, and PCT was measured in an immunoluminometric assay (ILMA), which was specifically developed for this study. PCT concentrations above 0.2 ng/g of wet tissue were found in a variety of organs in LPS treated baboons, but not in the control baboon. Organs and tissues with the highest PCT concentration included liver, kidney, aorta, fat, ovaries, bladder and adrenal gland. RT-PCR confirmed an extrathyroidal origin of PCT. Importantly, CT-mRNA expression was found in liver, lung, kidney, adrenal, colon, skin, spleen, brain and pancreas. In conclusion, our data confirm previous findings in hamsters, indicating an extrathyroidal origin for PCT in sepsis. Our primate model offers a valuable tool for further investigation of PCT's pathophysiological role and its immunoneutralization as a therapy for sepsis.
Morgenthaler
N G
NG
Research Department, B.R.A.H.M.S AG, Biotechnology Center Hennigsdorf/Berlin, Neuensdorfstrasse 25, 16761 Hennigsdorf/Berlin, Germany. n.morgenthaler@brahms.de
Struck
J
J
Chancerelle
Y
Y
Weglöhner
W
W
Agay
D
D
Bohuon
C
C
Suarez-Domenech
V
V
Bergmann
A
A
Müller
B
B
D000818:Animals; D002116:Calcitonin / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D010215:Papio; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
D008070:Lipopolysaccharides; D011498:Protein Precursors; D012333:RNA, Messenger; D002116:Calcitonin