Expression and secretion of procalcitonin and calcitonin gene-related peptide by adherent monocytes and by macrophage-activated adipocytes*

Linscheid, Philippe; Seboek, Dalma; Schaer, Dominik J.; Zulewski, Henryk; Keller, Ulrich; Müller, Beat

doi:10.1097/01.ccm.0000134404.63292.71

Cited by 266 publications

(198 citation statements)

References 29 publications

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“…Identifying the peripheral function of these components is complex, because the peptide and its receptor are present both in intrinsic and extrinsic primary sensory afferent neurons (10,11). Moreover, CGRP is produced by and activates migratory cells such as lymphocytes, granulocytes, and monocytes (12)(13)(14). Receptors for CGRP may be induced by intestinal inflammation, as is the substance P neurokinin 1 receptor in T cells and in intestinal epithelial cells (3,15).…”

mentioning

confidence: 99%

Local injection of dsRNA targeting calcitonin receptor-like receptor (CLR) ameliorates Clostridium difficile toxin A-induced ileitis

Bhargava¹,

Clifton²,

Mhaske³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Enteritis caused by Clostridium difficile toxin (Tx) is a nosocomial disease of increasing clinical concern, but the local mediators of C. difficile TxA inflammation are unknown. The potent vasodilator calcitonin gene-related peptide mediates neurogenic inflammation via the calcitonin receptor-like receptor (CLR). Here we examined the ileum-specific effects of reducing CLR on TxA ileitis by local preinjection of double-stranded RNAs. Treatment with CLR dsRNA for 7 d decreased CLR immunoreactivity, whereas treatment with non-CLR dsRNA did not. Subsequent injection of TxA in the same location increased CLR in rats treated with non-CLR dsRNA but not in rats treated with CLR dsRNA, documenting that local injection of dsRNA is effective in preventing the increase in CLR immunoreactivity in response to local TxA. After non-CLR dsRNA pretreatment, TxA induced robust intestinal secretion, myeloperoxidase activity, and histopathologic indications of inflammation including epithelial damage, congestion, neutrophil infiltration, loss of mucin from goblet cells, and increase in mast cell numbers. After CLR dsRNA pretreatment, TxA-induced changes in intestinal secretion and histopathologic inflammation were improved, including normal mucin staining and fewer resident mast cells. Loss of CLR prevented TxA-mediated activation of NF-κB and concomitant increases in pERK1/2 and TNF-α mRNA. Locally produced CLR plays a proinflammatory role in TxA ileitis via MAPK signaling and TNF-α. The results reported here strongly suggest that a local injection of dsRNA targeting CLR could be an effective local therapeutic approach at the inflammation site in the treatment of a growing, clinically relevant hospital-acquired disease, C. difficile infection.

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mentioning

confidence: 99%

Local injection of dsRNA targeting calcitonin receptor-like receptor (CLR) ameliorates Clostridium difficile toxin A-induced ileitis

Bhargava¹,

Clifton²,

Mhaske³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Indeed, Linscheid et al (15) reported a transient elevation in PCT mRNA expression by human peripheral blood monocytes immediately after adherence to endothelial cells or plastic surfaces. Furthermore, expression of calcitonin or calcitonin gene-related peptide 1 was noted in adipose tissue biopsies but not in leukocytes isolated from patients with high serum levels of PCT (15,38). In coculture experiments, adipocyte calcitonin mRNA expression was stimulated by E. coli-activated macrophages in which calcitonin mRNA was undetectable (15).…”

Section: Discussionmentioning

confidence: 96%

Procalcitonin in Children with Escherichia coli O157:H7 Associated Hemolytic Uremic Syndrome

et al. 2006

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Shiga toxin producing Escherichia coli (STEC) are noninvasive enteric pathogens that may cause hemorrhagic colitis (HC) and diarrhea-associated hemolytic uremic syndrome (Dϩ HUS). We hypothesized that development of Dϩ HUS is associated with increased serum procalcitonin (PCT) levels. PCT was measured by an immunoluminometric assay in 113 patients. Concentrations of PCT were different in normal controls, disease control groups (rotavirus enteritis, HC due to non-STEC pathogens, chronic renal failure), and children with uncomplicated O157:H7 HC or Dϩ HUS. Children with Dϩ HUS showed higher PCT levels than those with uncomplicated O157:H7 HC, and increased concentrations were noted in cases requiring peritoneal dialysis. Severely increased concentrations were observed in children with Dϩ HUS on d 5 or 6 after the onset of enteritis, whereas serial measurements in those with uncomplicated O157:H7 HC remained within the normal range throughout the first week of illness. PCT was correlated with serum concentrations of lipopolysaccharide (LPS)-binding protein and serum levels of alanine aminotransferase. Using two separate sets of real-time PCR primers, we were unable to detect elevated PCT mRNA transcripts in nonadherent undifferentiated (monocytic) or differentiated (macrophage-like) THP-1 cells stimulated with purified Shiga toxin-1 and/or LPS. Our data show that serum levels of PCT are associated with the severity of illness in children with Dϩ HUS. Further studies are needed to determine the role of PCT in the pathogenesis of thrombotic microangiopathy associated to childhood Dϩ HUS. (Pediatr Res 59: 579-583, 2006)

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“…Two isoforms of calcitonin gene-related peptide (CGRP), alpha-CGRP and beta-CGRP, are widely expressed in serum. 31,32 To study the selectivity of this assay, we tested the cross-reactivity of PCT to both isoforms of calcitonin; and our assay exhibited a little cross-reactivity, which was acceptable for the analysis.…”

Section: Discussionmentioning

confidence: 99%

Determining the Concentration of Procalcitonin Using a Magnetic Particles-based Chemiluminescence Assay for the Clinical Diagnosis of Sepsis

Rao

et al. 2013

ANAL. SCI.

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Our objective is to develop an assay based on magnetic particles (MPs) to determine the concentration of procalcitonin (PCT) using a chemiluminescence immunoassay (CLIA). Fluorescein isothiocyanate (FITC) and N-(aminobutyl)-N-(ethylisoluminol) (ABEI) were used to label two different anti-procalcitonin (PCT) monoclonal antibodies. The labeled antibodies, the PCT antigen, and the anti-FITC antibody-coated MPs formed a double-sandwiched immunocomplex. The measured relative light units (RLUs) of ABEI in the substrate solution were directly proportional to the amount of PCT present in the samples. The proposed method was linear to 600 ng/mL with a detection limit of 0.03 ng/mL. The coefficient of variation (CV) was <5% and <6% for the intra-and inter-assay precision, respectively. The average recoveries were between 95 and 107%. The linearity-dilution effect gave a linear correlation coefficient of 0.9912. This proposed assay provided an alternative method to quantitatively measure PCT in serum for the diagnosis of sepsis.

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Expression and secretion of procalcitonin and calcitonin gene-related peptide by adherent monocytes and by macrophage-activated adipocytes*

Cited by 266 publications

References 29 publications

Local injection of dsRNA targeting calcitonin receptor-like receptor (CLR) ameliorates Clostridium difficile toxin A-induced ileitis

Local injection of dsRNA targeting calcitonin receptor-like receptor (CLR) ameliorates Clostridium difficile toxin A-induced ileitis

Procalcitonin in Children with Escherichia coli O157:H7 Associated Hemolytic Uremic Syndrome

Determining the Concentration of Procalcitonin Using a Magnetic Particles-based Chemiluminescence Assay for the Clinical Diagnosis of Sepsis

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