Expression and secretion of procalcitonin and calcitonin gene-related peptide by adherent monocytes and by macrophage-activated adipocytes.
OBJECTIVE
To explore the roles of peripheral blood mononuclear cells (PBMCs) and PBMC-derived macrophages in sepsis-related increased procalcitonin and calcitonin gene-related peptide (CGRP) I production.


METHODS
Prospective, in vitro primary human cell culture study and human tissue samples gene expression analysis.


METHODS
University hospital research laboratories.


METHODS
Cells from healthy donors and septic patients.


METHODS
PBMCs were obtained from healthy donors. Isolation of pure monocyte cultures was performed by magnetic depletion of nonmonocyte cells from PBMCs. Adipose tissue biopsies and circulating leukocytes were collected from septic patients. Expressions of calcitonin messenger RNA and CGRP I messenger RNA were analyzed using reverse transcriptase-polymerase chain reaction and quantitative real-time polymerase chain reaction. Supernatant procalcitonin and CGRP protein content were determined by ultrasensitive chemiluminometric and radioimmunoassays, respectively.


RESULTS
PBMCs expressed and secreted procalcitonin and CGRP within 3-5 hrs after adherence to endothelial cells or plastic surfaces. This induction was transient, as it was not detectable after 18 hrs. No calcitonin or CGRP I messenger RNA was observed in leukocytes obtained from septic patients with markedly increased serum procalcitonin concentrations. Stimulation with cytokines, endotoxin, or Escherichia coli did not induce expression of calcitonin and CGRP I messenger RNA in PBMC-derived macrophages. However, inflammatory factors released from activated macrophages induced a marked expression of procalcitonin and CGRP in co-cultured human adipocytes.


CONCLUSIONS
The adhesion-induced, transient expression and secretion of procalcitonin and CGRP in vitro may play an important role during monocyte adhesion and migration in vivo. PBMC-derived macrophages may contribute to the marked increase in circulating procalcitonin by recruiting parenchymal cells within the infected tissue, as exemplified with adipocytes.
Department of Research, Division of Endocrinology, Diabetology and Clinical Nutrition, University Hospital, Basel, Switzerland.
Philippe
P
Linscheid
Dalma
D
Seboek
Dominik J
DJ
Schaer
Henryk
H
Zulewski
Ulrich
U
Keller
Beat
B
Müller
D017667:Adipocytes / Q000378:metabolism*; D002116:Calcitonin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000097:blood; D012016:Reference Values; D018805:Sepsis / Q000097:blood / Q000276:immunology
C000606589:CALCA protein, human; D011498:Protein Precursors; D012333:RNA, Messenger; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide