Functional and clinical aspects of the myelomonocyte protein calprotectin.

Johne, Berit; Fagerhol, Magne K.; Lyberg, Torstein; Prydz, Hans; Brandtzæg, Per; Næss-Andresen, Carl Fredrik; Dale, Inge

doi:10.1136/mp.50.3.113

Cited by 321 publications

(301 citation statements)

References 121 publications

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“…Bacteria are thought to contain high-affinity zinc transporters as a strategy to overcome zinc limitation during infection in which the acute phase response has been shown to result in reduced plasma zinc concentrations (20,38) with upregulation and release of the zinc binding complex calprotectin in the blood and lungs (29,31,55). In accord with this hypothesis, we demonstrated here that H. influenzae requires a specialized high-affinity zinc utilization pathway for virulence.…”

Section: Discussionsupporting

confidence: 76%

A Novel Zinc Binding System, ZevAB, Is Critical for Survival of Nontypeable Haemophilus influenzae in a Murine Lung Infection Model

et al. 2011

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Nontypeable Haemophilus influenzae (NTHI) is a Gram-negative bacterial pathogen that causes upper and lower respiratory infections. Factors required for pulmonary infection by NTHI are not well understood. Previously, using high-throughput insertion tracking by deep sequencing (HITS), putative lung colonization factors were identified. Also, previous research indicates that secreted disulfide-dependent factors are important for virulence of H. influenzae. In the present study, HITS data were compared with an informatics-based list of putative substrates of the periplasmic oxidoreductase DsbA to find and characterize secreted virulence factors. This analysis resulted in identification of the "zinc binding essential for virulence" (zev) locus consisting of zevA (HI1249) and zevB (HI1248). NTHI mutants of zevA and zevB grew normally in rich medium but were defective for colonization in a mouse lung model. Mutants also exhibited severe growth defects in medium containing EDTA and were rescued by supplementation with zinc. Additionally, purified recombinant ZevA was found to bind to zinc with high affinity. Together, these data demonstrate that zevAB is a novel virulence factor important for zinc utilization of H. influenzae under conditions where zinc is limiting. Furthermore, evidence presented here suggests that zinc limitation is likely an important mechanism for host defense against pathogens during lung infection.

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Section: Discussionsupporting

confidence: 76%

A Novel Zinc Binding System, ZevAB, Is Critical for Survival of Nontypeable Haemophilus influenzae in a Murine Lung Infection Model

et al. 2011

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“…Previous studies demonstrated its usefulness in active rheumatic disease [5,11], cystic fibrosis [12], pulmonary infections [13], and several other diseases [2]. In all cases the differences between normal and pathological levels suggested a diagnostic potential for Cal assay.…”

Section: Discussionmentioning

confidence: 84%

“…Calprotectin (Cal) is a calcium binding protein belonging to the S-100 protein family and derived predominantly from neutrophils and monocytes [1,2]. Various biological functions have been ascribed to Cal, including regulation in the inflammatory process [3] and antimicrobial activity [4].…”

Section: Introductionmentioning

confidence: 99%

“…Cal concentration is elevated in acute inflammatory reactions, and in some instances a correlation between Cal and other inflammation paramenters such as C reactive protein (CRP), erythrocyte sedimentation rate, and neutrophil granulocyte count has been shown [5]. As Cal is found in all tissues of the human body, its assessment in several fluids could distinguish between normal and pathological conditions [2]. For instance, an elevated Cal concentration in stools is considered a marker of intestinal neoplasias [6] or inflammatory bowel diseases [7] and helps to distinguish between organic causes of chronic diarrhea and irritable bowel syndrome [8].…”

Section: Introductionmentioning

confidence: 99%

“…An increased concentration of Cal in the plasma has been found in several organic diseases and suggests a diagnostic potential for Cal assay [2]. Despite these very promising data, no studies on the plasma Cal concentration in patients with acute pancreatits (AP) have been performed to date.…”

Section: Introductionmentioning

confidence: 99%

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Plasma Calprotectin Levels in Patients Suffering from Acute Pancreatitis

Carroccio

Rocco²,

Rabitti³

et al. 2006

Dig Dis Sci

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Calprotectin (Cal) concentration is elevated in acute inflammatory reactions and its increase in the plasma suggests a diagnostic potential for Cal assay. This study aimed (a) to evaluate the Cal plasma levels in patients suffering from acute pancreatitis (AP) and (b) to assess whether early assay of Cal plasma levels can be helpful in assessment of the severity of AP. Forty-six consecutive patients, median age 45 years, suffering from a first attack of AP were recruited at two medical centers. Data collected on admission included age, sex, delay between pain onset and admission, and Glasgow score. A severe outcome was defined according to the Atlanta criteria. AP was defined as edematous or necrotic according to the CT findings. Plasma Cal and serum C reactive protein (CRP) were assayed in all patients within the first 24 hr after hospitalization. Sixty subjects suffering from blood hypertension were recruited as controls. Plasma Cal was measured by a commercial ELISA system. In all AP patients and in none of the controls, plasma Cal concentration was higher than the normal limit. Cal values in AP pa- tients were significantly higher than in controls (P < 0.0001). There was not a statistically significant difference in Cal values between patients with severe and patients with mild AP. Plasma Cal values did not differ in necrotizing and edematous AP. During the follow-up plasma Cal was reassayed in six of the patients with abdominal fluid collection and the values were higher in the two patients with infected necrosis. We conclude that plasma Cal is elevated in patients with AP but it is not a useful marker for early prediction of pancreatitis severity. Further studies could evaluate its usefulness in pancreatic infected necrosis.

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