Plasma and BAL Fluid Concentrations of Antimicrobial Peptides in Patients With Mycobacterium avium- intracellulare Infection

Ashitani, Jun‐ichi; Mukae, Hiroshi; Hiratsuka, Takeaki; Nakazato, Masamitsu; Kumamoto, Kenshi; Matsukura, Shigeru

doi:10.1378/chest.119.4.1131

Cited by 57 publications

(39 citation statements)

References 27 publications

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“…6). Because hBD2 has been associated with immune responses against M. tuberculosis (16,20,31), and hBD2-transfected macrophages restrict the growth of intracellular M. tuberculosis (32), our results suggest a mechanism by which oxygen limitation triggers hBD2, resulting in reduced multiplication of tubercle bacilli. In contrast, cathelicidin, which was shown to mediate VDR-dependent killing of M. tuberculosis (17), was downregulated under oxygen-limiting conditions.…”

Section: Discussionmentioning

confidence: 71%

Hypoxia Triggers the Expression of Human β Defensin 2 and Antimicrobial Activity against Mycobacterium tuberculosis in Human Macrophages

Nickel

Busch

Mayer

et al. 2012

The Journal of Immunology

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Low oxygen tension is a metabolic hallmark of chronic infection. To investigate the influence of hypoxia on macrophage biology, we analyzed the interaction between the intracellular pathogen Mycobacterium tuberculosis and primary human macrophages. Although the metabolic activity of extracellular M. tuberculosis was reduced at oxygen levels between 0.5 and 10%, the bacilli remained viable throughout the 4 d of culture. Phagocytosis of virulent M. tuberculosis and the pathogen-induced release of inflammatory cytokines by macrophages were not affected by oxygen levels as low as 1%. However, we detected the upregulation of an antimicrobial effector pathway mediated by the vitamin D receptor and human β defensin 2. This finding was functionally relevant, because intracellular mycobacterial growth was inhibited by 58 ± 8% at 1% O2. We conclude that a hypoxic microenvironment, which is characteristic of infected tissue, supports the efficacy of antimicrobial immunity, in part by the upregulation of the antimicrobial peptide human β defensin 2.

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Section: Discussionmentioning

confidence: 71%

Hypoxia Triggers the Expression of Human β Defensin 2 and Antimicrobial Activity against Mycobacterium tuberculosis in Human Macrophages

Nickel

Busch

Mayer

et al. 2012

The Journal of Immunology

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“…The current authors previously determined the concentrations of three additional defensins (HNP-1, hBD-1 and hBD-2) in the serum and bronchoalveolar lavage (BAL) fluid during pulmonary disease states [9,[24][25][26][27][28][29]. The concentrations of both HNP-1 and hBD-2 increased in the serum and BAL fluid during the acute phase of respiratory infections, returning to basal levels after the completion of therapy [25][26][27].…”

Section: Discussionmentioning

confidence: 99%

“…The concentrations of both HNP-1 and hBD-2 increased in the serum and BAL fluid during the acute phase of respiratory infections, returning to basal levels after the completion of therapy [25][26][27]. Serum HNP-1 and hBD-2 concentrations also increased in noninfectious pulmonary diseases, including idiopathic pulmonary fibrosis [27] and diffuse panbronchiolitis [24,29].…”

Section: Discussionmentioning

confidence: 99%

Identification of hBD-3 in respiratory tract and serum: the increase in pneumonia

Ishimoto

Mukae²,

Date³

et al. 2006

Eur Respir J

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Human b-defensin (hBD)-3, a 45 amino acid antimicrobial peptide, was originally isolated from human skin. hBD-3 mRNA has also been detected in the airways by RT-PCR. While hBD-3 may be involved in antimicrobial defences within the respiratory tract, the presence of hBD-3 peptide in the respiratory system has not yet been confirmed.The antimicrobial activity of the synthesised hBD-3 peptide was measured by a radial diffusion assay and a colony count assay. The present authors confirmed the presence of hBD-3 peptide in homogenates of human lung and serum using reverse-phase HPLC coupled with a highly sensitive RIA. The localisation of the hBD-3 peptide was investigated by immunohistochemistry. In addition, the serum concentrations of hBD-3 were measured by RIA.hBD-3 exhibited a strong antimicrobial activity, which was unaffected by increasing salt concentrations. Immunohistochemically, the current authors observed the expression of hBD-3 in bronchial and bronchiolar epithelial cells. The mean¡SD serum concentration of hBD-3 in patients with bacterial pneumonia was 239.4¡17.8 pg?mL -1 in the acute phase and, decreased to 159.3¡20.1 pg?mL -1 after the completion of therapy.In conclusion, these findings will help elucidate the role of human b-defensin-3 in host immune responses and identify the pathophysiological significance of this molecule in respiratory infections.

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“…reported (19,20), and we recently investigated the presence of α-defensins 1-4 in BALFs of premature newborns with and without pneumonia (21): they were more expressed in cases of bacterial and fungal pneumonia, suggesting that they could be involved in innate host defense of the lung against microbial infection in preterm newborns. S100A8 and S100A12, together with S100A9, are members of the subgroup of S100A proteins named calgranulins.…”

mentioning

confidence: 99%

Association of high levels of α-defensins and S100A proteins with Candida mannan detection in bronchoalveolar lavage fluid of preterm neonates

et al. 2013

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Background: Candida mannan (Mn) detection in bronchoalveolar lavage fluid (BALF) was shown to be useful for earlier identification and preemptive therapy targeting in preterm infants at high risk of invasive Candida infection. We investigated whether early detection of Candida Mn in BALF is associated with the presence of some neutrophilic products, as markers of prenatal infection/inflammation. Methods: BALF specimens were collected during the first 48 h of life from mechanically ventilated preterm newborns. Samples were analyzed by high-performance liquid chromatography-electrospray ionization-mass spectrometry. The relative amounts of α-defensins 1-4 and S100A proteins were measured by extracted ion current peak area. Absolute and differential white cell counts in BALF were obtained. Mn antigen concentrations were determined by the Platelia Candida antigen kit. results: Twenty-five studied neonates were divided into two groups: Mn-positive group and Mn-negative group. Levels of α-defensins 1-4 and S100A12 were significantly higher in the Mn-positive group than in the Mn-negative group. Moreover, positive significant correlations between the absolute number of neutrophils and the levels of α-defensins 1-4 and S100A8 were observed. conclusion: The detection of Mn antigen in BALF of preterm infants is consistent with evidence of an innate immune response in their lungs as demonstrated by higher levels of α-defensins and S100A proteins.

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Plasma and BAL Fluid Concentrations of Antimicrobial Peptides in Patients With Mycobacterium avium- intracellulare Infection

Cited by 57 publications

References 27 publications

Hypoxia Triggers the Expression of Human β Defensin 2 and Antimicrobial Activity against Mycobacterium tuberculosis in Human Macrophages

Hypoxia Triggers the Expression of Human β Defensin 2 and Antimicrobial Activity against Mycobacterium tuberculosis in Human Macrophages

Identification of hBD-3 in respiratory tract and serum: the increase in pneumonia

Association of high levels of α-defensins and S100A proteins with Candida mannan detection in bronchoalveolar lavage fluid of preterm neonates

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