Isolation of human β-defensin-4 in lung tissue and its increase in lower respiratory tract infection

BackgroundHuman β-defensin-4 (hBD-4), a new member of the β-defensin family, was discovered by an analysis of the genomic sequence. The objective of this study was to clarify hBD-4 expression in human lung tissue, along with the inducible expression in response to infectious stimuli, localization, and antimicrobial activities of hBD-4 peptides. We also investigated the participation of hBD-4 in chronic lower respiratory tract infections (LRTI) by measuring the concentrations of hBD-4 peptides in human bronchial epithelial lining fluid (ELF).MethodsThe antimicrobial activity of synthetic hBD-4 peptides against E. coli and P. aeruginosa was measured by radial diffusion and colony count assays. We identified hBD-4 in homogenated human lung tissue by reverse-phase high-performance liquid chromatography coupled with a radioimmunoassay (RIA). Localization of hBD-4 was studied through immunohistochemical analysis (IHC). We investigated the effects of lipopolysaccharide (LPS) on hBD-4 expression and its release from small airway epithelial cells (SAEC). We collected ELF from patients with chronic LRTI using bronchoscopic microsampling to measure hBD-4 concentrations by RIA.ResultshBD-4 exhibited salt-sensitive antimicrobial activity against P. aeruginosa. We detected the presence of hBD-4 peptides in human lung tissue. IHC demonstrated the localization of hBD-4-producing cells in bronchial and bronchiolar epithelium. The levels of hBD-4 peptides released from LPS-treated SAECs were higher than those of untreated control cells. ELF hBD-4 was detectable in 4 of 6 patients with chronic LRTI, while the amounts in controls were all below the detectable level.ConclusionThis study suggested that hBD-4 plays a significant role in the innate immunity of the lower respiratory tract.

• Publication year

  2005

• Venue

  Respiratory Research

• Publication date

  2005-11-04

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/1465-9921-6-130PMID 16269090PMCID 1298335
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Differential effects of alpha- and beta-defensin on cytokine production by cultured human bronchial epithelial cells.

  2005cited by this paper
• Gram-negative bacterial resistance: evolving patterns and treatment paradigms.

  2005cited by this paper
• Differential effects of (cid:1) - and (cid:2) -defensin on cytokine production by cultured human bronchial epithelial cells

  2005cited by this paper
• Increased concentrations of human β-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis

  2003cited by this paper
• Isolation and Characterization of Human β-Defensin-3, a Novel Human Inducible Peptide Antibiotic*

  2001influential reference
• Salt-independent abnormality of antimicrobial activity in cystic fibrosis airway surface fluid.

  2001cited by this paper
• Human beta-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity.

  2001influential reference
• NOSOCOMIAL PNEUMONIA: Diagnostic and Therapeutic Considerations

  2001cited by this paper
• New bronchoscopic microsample probe to measure the biochemical constituents in epithelial lining fluid of patients with acute respiratory distress syndrome

  2001cited by this paper
• Identification of a novel, multifunctional beta-defensin (human beta-defensin 3) with specific antimicrobial activity. Its interaction with plasma membranes of Xenopus oocytes and the induction of macrophage chemoattraction.

  2001cited by this paper
• Identification of a novel, multifunctional β-defensin (human β-defensin 3) with specific antimicrobial activity

  2001influential reference
• Mucoid Pseudomonas aeruginosa, TNF- α , and IL-1 β , but Not IL-6, Induce Human β -Defensin-2 in Respiratory Epithelia

  2000cited by this paper
• Epithelial antimicrobial peptides in host defense against infection

  2000influential reference
• Mucoid Pseudomonas aeruginosa, TNF-alpha, and IL-1beta, but not IL-6, induce human beta-defensin-2 in respiratory epithelia.

  2000cited by this paper
• Transcriptional Regulation of β-Defensin Gene Expression in Tracheal Epithelial Cells

  2000cited by this paper
• Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung.

  1998influential reference
• Human beta-defensin-1: an antimicrobial peptide of urogenital tissues.

  1998cited by this paper
• Production of β-defensins by human airway epithelia

  1998cited by this paper
• Identification of human beta-defensin-2 in respiratory tract and plasma and its increase in bacterial pneumonia.

  1998cited by this paper
• Production of beta-defensins by human airway epithelia.

  1998cited by this paper
• Human β-Defensin-1 Is a Salt-Sensitive Antibiotic in Lung That Is Inactivated in Cystic Fibrosis

  1997cited by this paper
• A peptide antibiotic from human skin

  1997cited by this paper
• Widespread expression of beta‐defensin hBD‐1 in human secretory glands and epithelial cells

  1996cited by this paper
• Evaluation of susceptibility of gram-positive and -negative bacteria to human defensins by using radial diffusion assay

  1996cited by this paper
• Diagnostic and Therapeutic Considerations

  1996cited by this paper
• hBD-1: a novel beta-defensin from human plasma.

  1995cited by this paper
• hBD‐1: a novel β‐defensin from human plasma

  1995cited by this paper
• Neutrophil defensins: purification, characterization, and antimicrobial testing.

  1994cited by this paper
• Emergence and persistence of Pseudomonas aeruginosa in the cystic fibrosis airway.

  1992cited by this paper
• Molecular forms of atrial natriuretic polypeptides in mammalian tissues and plasma.

  1985cited by this paper
• Regional distribution of adrenorphin in rat brain: comparative study with PH-8P.

  1984cited by this paper

• Lung antimicrobial proteins and peptides: From host defense to therapeutic strategies.

  2024cites this paper
• Characterization of Tissue Immunity Defense Factors of the Lip in Primary Dentition Children with Bilateral Cleft Lip Palate

  2024cites this paper
• Potential application of andrographolide in vital pulp therapy by inducing expression of human β defensin 4

  2024cites this paper
• Preventing Respiratory Viral Diseases with Antimicrobial Peptide Master Regulators in the Lung Airway Habitat

  2023cites this paper
• Local Defense Factors in Cleft-Affected Palate in Children before and during Milk Dentition Age: A Pilot Study

  2023cites this paper
• Antimicrobial Peptides and Interleukins in Cleft Soft Palate

  2023cites this paper
• Glycosaminoglycan, Antimicrobial Defence Molecule and Cytokine Appearance in Tracheal Hyaline Cartilage of Healthy Humans

  2022cites this paper
• Human beta-defensins 2 and 4 are dysregulated in patients with coronavirus disease 19

  2021cites this paper
• Human tear fluid modulates the Pseudomonas aeruginosa transcriptome to alter antibiotic susceptibility.

  2021cites this paper
• Local Defence System in Healthy Lungs

  2021cites this paper
• Antimicrobial peptides in hidradenitis suppurativa: a systematic review *

  2021cites this paper
• Potential Application of Human β-Defensin 4 in Dental Pulp Repair

  2020cites this paper
• Proliferation Markers, Remodeling Factors, Cytokines, Antimicrobial Peptides and Gene Proteins in Cholesteatoma

  2020cites this paper
• Profiling the susceptibility of Pseudomonas aeruginosa strains from acute and chronic infections to cell-wall-targeting immune proteins

  2019cites this paper
• An Insight into COPD Morphopathogenesis: Chronic Inflammation, Remodeling, and Antimicrobial Defense

  2019cites this paper
• ATP serves an anti-inflammatory role by enhancing β-defensin-2 response in acute pneumonia of rat

  2017cites this paper
• β-Defensins in the Fight against Helicobacter pylori

  2017influential citation
• Role of Soluble Innate Effector Molecules in Pulmonary Defense against Fungal Pathogens

  2017cites this paper
• Cystic Fibrosis – Renewed Hopes Through Research 440 Consensus is growing on sphingolipids ( SLs ) as novel targets to cure pulmonary disorders including CF , since modulation of cellular ceramide reduces lung inflammation

  2017cites this paper
• The role of natural antimicrobial peptides during infection and chronic inflammation

  2017cites this paper
• Candida Infections and Human Defensins.

  2017cites this paper
• Phenotypic Consequences of β-Defensin Copy Number Variation in Humans

  2016cites this paper
• Host Defense Peptides and Their Advancements in Translational Staphylococcus aureus Research

  2016cites this paper
• Function of Antimicrobial Peptides in Lung Innate Immunity

  2016cites this paper
• Host Defense Peptides and Their Potential as Therapeutic Agents

  2016cites this paper
• Mammalian Antimicrobial Peptides: Promising Therapeutic Targets Against Infection and Chronic Inflammation.

  2015cites this paper
• Copy Number Variation of the Beta-Defensin Genes in Europeans: No Supporting Evidence for Association with Lung Function, Chronic Obstructive Pulmonary Disease or Asthma

  2014cites this paper
• Does dysregulation of immune responses in the tonsils play an important role in the pathology of psoriasis

  2014cites this paper
• Regulation and function of antimicrobial peptides in immunity and diseases of the lung.

  2014cites this paper
• A new technique of bronchial microsampling and proteomic analysis of epithelial lining fluid in a rat model of acute lung injury.

  2014cites this paper
• [110th Scientific Meeting of the Japanese Society of Internal Medicine: Invited lecture: 3. In pursuit of overcoming pneumonia].

  2013cites this paper
• Antimicrobial peptides: The natural proteins and the future application for treatment of infectious diseases

  2013cites this paper
• Immunohistochemical localization of beta defensins in the endometrium of rat uterus during the postpartum involution period

  2012cites this paper
• Pharmacological Modulators of Sphingolipid Metabolism for the Treatment of Cystic Fibrosis Lung Inflammation

  2012cites this paper
• Antimicrobial peptide defensin: Identification of novel isoforms and the characterization of their physiological roles and their significance in the pathogenesis of diseases

  2012cites this paper
• Human β-defensin-2 and psoriasin, two new innate immunity targets of zinc gluconate.

  2012cites this paper
• Doctorate School in Molecular Medicine Doctorate Program in Genetics and Molecular Medicine Coordinator: Prof. Lucio Nitsch XXIV Cycle "Antimicrobial Activity and Cell Toxicity of Human Beta Defensins and Their Newly Synthesized Analogs "

  2011cites this paper
• INFLAMMATORY MECHANISMS OF CHEMOKINE RECEPTOR 7 EXPRESSION IN METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK (SCCHN)

  2011cites this paper
• KL‐6 and CEA levels in epithelial lining fluid microsamples predict response to gefitinib in patients with advanced non‐small cell lung cancer

  2011cites this paper
• Modulators of sphingolipid metabolism reduce lung inflammation.

  2011cites this paper
• The Airway Epithelium: Soldier in the Fight against Respiratory Viruses

  2011cites this paper
• S100A7/psoriasin expression in the human lung: unchanged in patients with COPD, but upregulated upon positive S. aureus detection

  2011cites this paper
• Candida famata modulates toll‐like receptor, β‐defensin, and proinflammatory cytokine expression by normal human epithelial cells

  2010cites this paper
• Normal Human Gingival Epithelial Cells Sense C. parapsilosis by Toll-Like Receptors and Module Its Pathogenesis through Antimicrobial Peptides and Proinflammatory Cytokines

  2010cites this paper
• Roles of human β-defensins in innate immune defense at the ocular surface: arming and alarming corneal and conjunctival epithelial cells

  2010cites this paper
• The Haemophilus ducreyi Sap transporter contributes to antimicrobial peptide resistance

  2009cites this paper
• Epidermal Reactions to Injury with Implications for Innate Immunity

  2009cites this paper
• Receptores de la inmunidad innata en procesos infecciosos pulmonares

  2009cites this paper
• Human β-defensins—at the front line of the peritonsillar abscess

  2009cites this paper
• Antimicrobial peptides in innate immune responses.

  2008cites this paper
• Enhanced expression of murine beta-defensins (MBD-1, -2,- 3, and -4) in upper and lower airway mucosa of influenza virus infected mice.

  2008cites this paper
• Review: Human antimicrobial proteins — effectors of innate immunity

  2007cites this paper
• The role of cathelicidin and defensins in pulmonary inflammatory diseases

  2007cites this paper
• Significance of human beta-defensins in the epithelial lining fluid of patients with chronic lower respiratory tract infections.

  2007cites this paper
• Significance of human β‐defensins in the epithelial lining fluid of patients with chronic lower respiratory tract infections

  2007cites this paper