Establishment of Radioimmunoassay for Human Neutrophil Peptides and Their Increases in Plasma and Neutrophil in Infection

Shiomi, Kazutaka; Nakazato, Masamitsu; Ihi, Toshihiko; Kangawa, Kenji; Matsuo, Hisayuki; Matsukura, Shigeru

doi:10.1006/bbrc.1993.2190

Cited by 68 publications

(54 citation statements)

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“…Our findings show that the IC 50 of HNP1 and HD5 on BKV infection was 23.2 and 9.1 g/ml, respectively. HNP1 levels in the human plasma range from 400 ng/ml in healthy individuals to 13 g/ml in individuals with bacteria infections and may be found in concentrations as high as 6 mg/ml within neutrophils (63)(64)(65)(66). Less is known about the concentration of HD5 in the small intestines, however, analysis of urethral lavages from men with gonorrhea infections show HD5 concentrations in inflamed genital tracts at 0.6 Ϯ 0.68 g/ml (17).…”

Section: Discussionmentioning

confidence: 99%

Human α-Defensins Inhibit BK Virus Infection by Aggregating Virions and Blocking Binding to Host Cells

Dugan

Maginnis

Jordan

et al. 2008

Journal of Biological Chemistry

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BK virus (BKV) is a polyomavirus that establishes a lifelong persistence in most humans and is a major impediment to success of kidney grafts. The function of the innate immune system in BKV infection and pathology has not been investigated. Here we examine the role of antimicrobial defensins in BKV infection of Vero cells. Our data show that ␣-defensin human neutrophil protein 1 (HNP1) and human ␣-defensin 5 (HD5) inhibit BKV infection by targeting an early event in the viral lifecycle. HD5 treatment of BKV reduced viral attachment to cells, whereas cellular treatment with HD5 did not. Colocalization studies indicated that HD5 interacts directly with BKV. Ultrastructural analysis revealed HD5-induced aggregation of virions. HD5 also inhibited infection of cells by other related polyomaviruses. This is the first study to demonstrate polyomavirus sensitivity to defensins. We also show a novel mechanism whereby HD5 binds to BKV leading to aggregation of virion particles preventing normal virus binding to the cell surface and uptake into cells.BK virus is a member of the polyomaviridae family. Polyomaviruses are small (40 -50 nm in diameter), non-enveloped, double-stranded DNA viruses that cause tumors in some species outside of their natural host range (1). BKV infects ϳ80 -90% of the human population and establishes a lifelong persistence within epithelial cells of the urinary tract (2, 3). Although BKV infection remains asymptomatic throughout the lifetime of most humans, immunocompromised individuals are susceptible to BKV-induced disease. Reactivation of BKV has been linked to hemorrhagic cystitis in bone marrow transplant recipients and is the etiological agent of polyomavirus-induced nephropathy (PVN), 2 a complication found in 5% of kidney transplant recipients (4, 5). In PVN, BKV induces interstitial nephritis resulting in graft destruction and leads to transplant failure in ϳ50% of diagnosed cases (6, 7). BKV reactivation causes a serious viral infection after renal transplantation and is a significant obstacle to the success of kidney grafts.The factors that contribute to BKV-induced disease are largely unknown. As only a subset of kidney transplant recipients develop PVN, this raises the question of what unique factors are present in these situations for pathogenesis to ensue? The factors that contribute to PVN likely comprise multiple conditions that involve the virus, the host, and the graft. Some risk factors for the development of PVN include male gender, older age, and higher number of HLA mismatches (7, 8). Epidemiological studies suggest that the most significant cofactor leading to PVN is the degree of immunosuppression. The rise in PVN diagnoses is directly correlated to the increased use of the more potent anti-rejection drugs, tacromilus and mycophenolate mofetil (9, 10). Currently, a reduction of immunosuppressive therapy is effectively used to decrease viral replication in PVN patients suggesting that a functional immune system is critical in controlling BKV replication and pathology (11). ...

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Section: Discussionmentioning

confidence: 99%

Human α-Defensins Inhibit BK Virus Infection by Aggregating Virions and Blocking Binding to Host Cells

Dugan

Maginnis

Jordan

et al. 2008

Journal of Biological Chemistry

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“…Lyophilised eluates were assayed by hBD-3-specific RIA. The serum concentrations of HNP-1, hBD-1 and hBD-2 were also assayed by previously established RIA methods [8,18,19]. Data are expressed as the mean¡SEM.…”

Section: Serummentioning

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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“…Neutrophil elastase was measured by enzyme immunoassay (Sanwa, Nagoya, Japan), and IL-1β levels were measured by radioimmunoassay (RIA) (Medgenix Diagnostics SA, Brussels, Belgium). In addition, defensin (human neutrophil peptides 1-3) levels were measured by RIA established by our group [9].…”

Section: Case Studymentioning

confidence: 99%

Neutrophil-related cytokines and neutrophil products in bronchoalveolar lavage fluid of a patient with ANCA negative Wegener's granulomatosis

Mukae¹,

Matsumoto²,

Ashitani³

et al. 1996

Eur Respir J

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N Ne eu ut tr ro op ph hi il l--r re el la at te ed d c cy yt to ok ki in ne es s a an nd d n ne eu ut tr ro op ph hi il l p pr ro od du uc ct ts s i in n b br ro on nc ch ho oa al lv ve eo ol la ar r l la av va ag ge e f fl lu ui id d o of f a a p pa at ti ie en nt t Peripheral blood neutrophilia was present but the anti-neutrophil cytoplasmic antibody (ANCA) was negative. The serum and BALF levels of neutrophil-related cytokines, including interleukin (IL)-8, granulocyte colony-stimulating factor (G-CSF) and IL-1β, were increased, particularly in BALF. Plasma and BALF levels of neutrophil elastase and defensins, which are released by neutrophils and are potentially toxic to cells, were also elevated.Our findings suggest that neutrophils and neutrophil-related cytokines may play an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody negative as well as anti-neutrophil cytoplasmic antibody positive Wegener's granulomatosis.

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Establishment of Radioimmunoassay for Human Neutrophil Peptides and Their Increases in Plasma and Neutrophil in Infection

Cited by 68 publications

References 0 publications

Human α-Defensins Inhibit BK Virus Infection by Aggregating Virions and Blocking Binding to Host Cells

Human α-Defensins Inhibit BK Virus Infection by Aggregating Virions and Blocking Binding to Host Cells

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

Neutrophil-related cytokines and neutrophil products in bronchoalveolar lavage fluid of a patient with ANCA negative Wegener's granulomatosis

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