Elevated Levels of α-Defensins in Plasma and BAL Fluid of Patients With Active Pulmonary Tuberculosis

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

doi:10.1378/chest.121.2.519

Cited by 70 publications

(61 citation statements)

References 29 publications

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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: 98%

“…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: 98%

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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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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

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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“…Some chronic lung inflammatory states are characterized by elevated levels of HNPs in BAL fluid (including tuberculosis (32) and ␣1-antitrypsin deficiency (33)). Very high levels of HNPs likely are present in the immediate vicinity of activated neutrophils.…”

Section: Discussionmentioning

confidence: 99%

“…Both ␣-and ␤-defensins are present in the respiratory tract and gastrointestinal tract, sites where they could potentially interact with SP-D (31). In humans, ␣-defensins are stored and released in large quantities from neutrophil granules during infectious and inflammatory states (32,33) and are referred to as human neutrophil peptides (HNP) 1, 2, or 3. HNPs are basic peptides 29 -30 aa in length.…”

Section: Nfluenza a Virus (Iav)mentioning

confidence: 99%

Innate Defense against Influenza A Virus: Activity of Human Neutrophil Defensins and Interactions of Defensins with Surfactant Protein D

Hartshorn

White

Tecle

et al. 2006

The Journal of Immunology

111

115

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Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection, in part by modifying interactions with neutrophils. Human neutrophil defensins (HNPs) inhibit infectivity of enveloped viruses, including IAV. Our goal in this study was to characterize antiviral interactions between SP-D and HNPs. Recombinant and/or natural forms of SP-D and related collectins and HNPs were tested for antiviral activity against two different strains of IAV. HNPs 1 and 2 did not inhibit viral hemagglutination activity, but they interfered with the hemagglutination-inhibiting activity of SP-D. HNPs had significant viral neutralizing activity against divergent IAV strains. However, the HNPs generally had competitive effects when combined with SP-D in assays using an SP-D-sensitive IAV strain. In contrast, cooperative antiviral effects were noted in some instances when relatively SP-D-resistant strains were treated with SP-D and HNPs. HNPs were found to bind to the neck and/or carbohydrate recognition domain of SP-D. This binding was specific because no, or minimal, binding to other collectins was found. HNPs precipitated SP-D from bronchoalveolar lavage fluid and reduced the antiviral activity of bronchoalveolar lavage fluid. HNP-1 and -2 differed somewhat in their independent antiviral activity and their binding to SP-D. These results are relevant to the early phase of host defense against IAV, and suggest a complex interplay between SP-D and HNPs at sites of active inflammation.

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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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Elevated Levels of α-Defensins in Plasma and BAL Fluid of Patients With Active Pulmonary Tuberculosis

Cited by 70 publications

References 29 publications

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

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

Innate Defense against Influenza A Virus: Activity of Human Neutrophil Defensins and Interactions of Defensins with Surfactant Protein D

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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