Calprotectin - A pleiotropic molecule in acute and chronic inflammation

Division of Immunology and Gnotobiology, Academy of Sciences of the Czech Republic, Praha, Praha, Czech Republic
Physiological research / Academia Scientiarum Bohemoslovaca (Impact Factor: 1.29). 02/2004; 53(3):245-53.
Source: PubMed


Calprotectin (MRP8/14, S100A8/S100A9, 27E10 antigen) is a heterodimer of two calcium-binding proteins present in the cytoplasm of neutrophils and expressed on the membrane of monocytes. Upon neutrophil activation or endothelial adhesion of monocytes, calprotectin is released and may be detected in serum or body fluids as potentially useful clinical inflammatory marker. The soluble form of calprotectin provides both bacteriostatic and cytokine-like effects in the local environment. When calprotectin metabolism is affected on a systemic level, the zinc-binding properties of protein may induce severe dysregulation of zinc homeostasis with severe clinical symptoms. The distribution of membrane form of calprotectin is restricted to monocytes and immature macrophages and the presence of calprotectin-positive infiltrating cells reflects the influx of mononuclear phagocytes to the site of inflammation. Calprotectin expression and release seems to be of particular importance in immune and immunopathological reactions.

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    • "According to Yui et al. This increase was caused by the migration of leukocytes in the region of inflammation and tissue disruption[26,27]. Thus, in colorectal cancer, inflammatory bowel disease, necrotizing enterocolitis and celiac diseases fecal Cal levels have increased. "
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    ABSTRACT: Background The aim of this study was to identify the diagnostic role of plasma calprotectin value for a distinction of presence acute appendicitis and the indifference of uncomplicated from complicated acute appendicitis. Methods Plasma calprotectin, white blood cell and C-reactive protein values of 89 patients, who have undergone laparoscopic appendectomy between January 2013 and May 2013 were evaluated. Results Calprotectin was 91 ng/mL (range 45–538) for acute appendicitis and 47 ng/ml (range 28–205) for the control group. There was a positive, statistically significant relation between calprotectin and C-reactive protein values (r = 0. 292 p = 0. 001, respectively). There was no statistically significant difference was determined between calprotectin and white blood cell values (r = 0. 142 p = 0. 187, respectively). CRP and Cal values were significantly higher in patients with a complicated AA group than in those with uncomplicated AA (p = 0. 014, p = 0. 0001, respectively) whereas white blood cell counts did not differ significantly between two groups (p = 0. 164). Conclusion Plasma calprotectin levels were increased in patients with acute appendicitis and should use in a distinction of uncomplicated from complicated acute appendicitis patients.
    Full-text · Article · Dec 2016 · World Journal of Emergency Surgery
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    • "cancer suggests that S100A8/A9 may play a key role in inflammation-associated cancer (Striz et al., 2004; Gebhardt et al., 2008). Calprotectin is resistant to enzymatic degradation and can be easily measured in stools. "
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    ABSTRACT: Background: Calprotectin in feces seems to be a more sensitive marker for gastrointestinal (GI) cancers than fecal occult blood, but its specificity may be too low for screening average risk populations. This study aims at evaluating the diagnostic value of fecal calprotectin as a screening biomarker for GI malignancies. Materials and methods: In a case-control study, 100 patients with GI malignancies (50 patients with colorectal cancer and 50 patients with gastric cancer) and 50 controls were recruited in Tabriz Imam Reza and Sina hospitals during a 24-month period. One to two weeks after the last endoscopy/colonoscopy, fecal specimens were collected by the patients and examined by ELISA method for quantitative measurement of calprotectin content. The results were compared between the three groups. Results: The mean fecal calprotectin level was 109.1 ± 105.3 (2.3-454.3, median:74), 241.1 ± 205.2 (3.4-610.0, median:19.3) and 45.9 ± 55.1 μg/g (1.3-257.1, median:19.3) in gastric cancer, colorectal cancer and control group, respectively, the differences being significant (p<0.001) and remaining after adjustment for age. The optimal cut-off point for fecal calprotectin was ≥ 75.8 μg/g for distinguishing colorectal cancer from normal cases (sensitivity and specificity of 80% and 84%, respectively). This value was ≥ 41.9 μg/g for distinguishing gastric cancer from normal cases (sensitivity and specificity of 62%). Conclusions: Our results revealed that fecal calprotectin might be a useful and non-invasive biomarker for distinguishing colorectal cancer from non-malignant GI conditions. However, due to low sensitivity and specificity, this biomarker may not help physicians distinguishing gastric cancer cases from healthy subjects.
    Full-text · Article · Feb 2014 · Asian Pacific journal of cancer prevention: APJCP
    • "In addition to MT, other Zn 21 binding proteins exist, including S100A8 and A9. Together they form the Zn 21 -binding heterodimeric protein calprotectin, which is expressed in high levels in myeloid cells, in particular in neutrophils [27] [28]. Its expression responds to zinc supplementation and deprivation and it is upregulated during calcitriol-induced monocyte differentiation, which depends on a reduction of free intracellular Zn 21 [29]. "
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    ABSTRACT: For more than 50 years, it has been known that zinc deficiency compromises immune function. During this time, knowledge about the biochemistry of zinc has continued to grow, but only recent years have provided in-depth molecular insights into the multiple aspects of zinc as a regulator of immunity. A network based on ZnT and ZIP proteins for transport and metallothionein for storage tightly regulates zinc availability, and virtually all aspects of innate and adaptive immunity are affected by zinc. In vivo, zinc deficiency alters the number and function of neutrophil granulocytes, monocytes, natural killer (NK)-, T-, and B-cells. T cell functions and balance between the different subsets are particularly susceptible to changes in zinc status. This article focuses in particular on the main mechanisms by which zinc ions exert essential functions in the immune system. On the one hand, this includes tightly protein bound zinc ions serving catalytic or structural functions in a multitude of different proteins, in particular enzymes and transcription factors. On the other hand, increasing evidence arises for a regulatory role of free zinc ions in signal transduction, especially in cells of the immune system. Identification of several molecular targets, including phosphatases, phosphodiesterases, caspases, and kinases suggest that zinc ions are a second messenger regulating signal transduction in various kinds of immune cells. © 2013 BioFactors, 2013.
    No preview · Article · Feb 2014 · BioFactors
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