Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “beta-Defensins”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1999

Antibacterial components in bronchoalveolar lavage fluid from healthy individuals and sarcoidosis patients.

Antibacterial peptides and proteins are an integral part of the epithelial defense barrier that provides immediate protection against bacterial invasion. In humans, alpha-defensins are mainly bactericidal effectors in circulating granulocytes, beta-defensin-1 is synthesized in epithelial cells, and LL-37 is produced in granulocytes but is also induced in skin epithelia during inflammation. To investigate the importance of these defense effectors in disease, we analyzed bronchoalveolar lavage fluid (BALF) for bactericidal activity. Antibacterial activity was found in BALF material from healthy individuals and sarcoidosis patients, with enhanced activity in BALF from the patients. The activity was present as several antibacterial components, of which we have so far characterized LL-37, lysozyme, alpha-defensins, and antileukoprotease. In addition, the antibacterial peptide LL-37 was located in alveolar macrophages, bronchial epithelial cells, and bronchial glands, suggesting that it has a defensive role in airway mucosa. In conclusion, the airway epithelium is protected by a complex antibacterial defense system. This is activated in sarcoidosis, and may explain why these patients seldom develop severe respiratory tract infections.

Adult↗
PubMed1998

The effect of chloride concentration on human neutrophil functions: potential relevance to cystic fibrosis.

Recently, some investigators have observed elevated concentrations of chloride in the airway surface fluid (ASF) overlying respiratory epithelia from cystic fibrosis (CF) patients compared with ASF overlying non-CF epithelia. Others have shown that this elevated ASF salt concentration can inactivate human beta-defensin-1, an antimicrobial peptide secreted by respiratory epithelia. This could impair the primary epithelial defense against bacteria in the CF airway, thereby forcing a greater reliance on polymorphonuclear leukocyte (PMN)-mediated defenses. Pseudomonas aeruginosa (Psa) flourishes in the CF airway despite the presence of abundant PMN. We therefore investigated whether elevated ASF chloride concentration in CF might also compromise PMN function. We employed a cell-culture model in which halide concentrations and osmolarity were varied independently. We examined the effects of chloride concentration on three aspects of PMN function: recruitment of PMN to the airway (production of interleukin-8 [IL-8]), PMN antimicrobial activity (killing of Psa), and PMN clearance from the airways (apoptosis and lysis). We found that exposure to elevated chloride concentration increased PMN synthesis of IL-8, decreased PMN killing of Psa, and accelerated PMN apoptosis and lysis. In CF airways, elevated chloride therefore could contribute to the increased number of PMN recruited into the airways, the increased survival of Psa, and the increased quantity of toxic mediators released by PMN into the airways. These effects of elevated chloride on PMN function may provide another causal link between loss of cystic fibrosis transmembrane conductance regulator function and CF lung disease.

Adult↗
PubMedDate not supplied

Multiple promoter and splicing mRNA variants of the epididymis-specific gene EP2.

The EP2 gene codes for a family of androgen-dependent, epididymis-specific secretory proteins. Using probes derived from human HE2 cDNA, a chimpanzee epididymal cDNA library was screened. Five variants of chimpanzee EP2 cDNA were identified. Variant 1 (EP2A) is the chimpanzee ortholog of HE2. Variant 2 (EP2B) has an alternative 5' end. Variant 3 (EP2C) has an alternative 3' end. Two additional variants were identified by reverse transcriptase-polymerase chain reaction analysis. Variant 4 (EP2D) and variant 5 (EP2E) appear to lack an exon, resulting in a shift in the open reading frame. Presumably, the 5 variants originate from the same gene and result from alternative promoters and alternative splicing. Each of the putative proteins encoded by these variant messages has a leader sequence characteristic for a secretory protein. After removal of the leader sequence, each of these proteins is predicted to consist of 1 or 2 out of 4 possible peptide modules. Two of these modules have no recognizable homology to known proteins. The other 2 modules have a distribution of cysteine residues characteristic for beta-defensins, a family of proteins with antimicrobial activity.

Alternative Splicing↗
PubMed1996

Systematic isolation of circulating human peptides: the concept of peptide trapping.

The structural determination of circulating human peptides is essential to determine their correct posttranslationally processed form. Human hemofiltrate from patients with end stage renal disease is accessible in large quantities and is used as a source for the preparation of circulating peptides. After complete peptide extraction from hemofiltrate, a systematic separation with different chromatographic techniques is achieved. Single peptides are selected according to their mass and chromatographic elution position. Following chromatographic purification, amino acid sequence analysis is performed in combination with data base search. The identification of circulating peptides leads to numerous fragments resulting from cleavage of larger plasma proteins as well as to the discovery of new peptide hormones. The results obtained so far give insight into the degradation of plasma proteins such as fibrinogen, which results in the generation of fragments with biological activity themselves and in the identification of a novel cytokine HCC-1, the first member of beta-defensins in humans, hBD-1, and different peptides not present in any data base.

Amino Acid Sequence↗
PubMed1998

Localization of expression of human beta defensin-1 in the pancreas and kidney.

Defensins are antimicrobial peptides which play a key role in innate immunity. High levels of human beta defensin-1 (hBD-1) have previously been detected in the kidney and pancreas, but the cell-specific location of hBD-1 mRNA has not been determined. The expression of hBD-1 mRNA has been examined in fetal and adult pancreas and kidney by mRNA in situ hybridization. In fetal pancreas, hBD-1 expression was detected in the developing acini and in adult pancreas in the acini, but not in the pancreatic ducts. In both fetal and adult kidney, hBD-1 expression was detected in the collecting ducts and in the loops of Henle in adult kidney. Expression of hBD-1 mRNA in the pancreas and kidney from early development and in the acini of the adult pancreas, rather than in the pancreatic ducts, may indicate that in these tissues, hBD-1 fulfils physiological functions in addition to host defence.

Adult↗
PubMed2000

[Antimicrobial peptides and peptide antibiotics].

Antimicrobial peptides are naturally occurring antibiotics. As part of the innate immune system of vertebrates they have direct antimicrobial function. Further, they can act as mediators of inflammation. Their antimicrobial spectrum covers gram-positive and -negative bacteria as well as fungi and certain viruses. Based on their structure, antimicrobial peptides can be divided into several families. Peptides of the defensin, cathelicidin, and histatin families have been isolated from humans, where they have been found in defense cells, such as macrophages or neutrophils, as well as in epithelial cells. Decreased production of antimicrobial peptides is associated with immune deficiencies. Further, lung disease in cystic fibrosis may be linked to the dysfunction of antimicrobial peptides. Based on naturally occurring antimicrobial peptides, derivates of these molecules were developed as innovative antibiotic drugs. The present review focuses on the biology of antimicrobial peptides as well as their potential as drugs.

Anti-Bacterial Agents↗
PubMed1991

Bactericidal potency and mechanistic specificity of neutrophil defensins against bovine mastitis pathogens.

Two neutrophil defensins, rabbit peptides NP-1 and NP-5, were examined for their in vitro antibacterial activity against a panel of Gram-positive and Gram-negative organisms isolated from mastitic cows. Incubation for 60 minutes with 5 micrograms/ml of NP-1 in 10 mM sodium phosphate buffer resulted in substantial killing (greater than 95%) of all organisms tested. Although NP-5 was virtually inactive under these same conditions, supplementation of the incubation mixture with dilute nutrient media sensitized otherwise resistant organisms to this defensin. For both NP-1 and NP-5, bactericidal activity was dependent on time and concentration. Our findings demonstrate that the spectrum of defensin bactericidal activities include clinically important bovine pathogens. Further, the data demonstrate that NP-1 and NP-5, peptides which are homologous in 18 of their 33 residue positions, possess distinct mechanisms of action.

Amino Acid Sequence↗
PubMed1999

A novel mouse beta defensin, Defb2, which is upregulated in the airways by lipopolysaccharide.

Studies have shown that beta defensins are present in the human airways and may be relevant to the pathogenesis of cystic fibrosis lung disease. Here we report the identification of a novel mouse gene, Defb2, which shows sequence similarity to previously described mouse and human airway beta defensins. Defb2 does not appear to be expressed in the airways of untreated mice but it is upregulated in response to lipopolysaccharide. The induced expression of this gene by an inflammatory stimulus strongly suggests that this defensin contributes to host defence at the mucosal surface of the airways.

Amino Acid Sequence↗
PubMed2000

Cell biology of tubotympanum in relation to pathogenesis of otitis media - a review.

The sterility of the eustachian tube and tympanic cavity of normal individuals is maintained not only by the adaptive immune system, but also by the mucociliary system and the antimicrobial molecules of innate immunity. Mucin production and periciliary fluid homeostasis are essential for normal mucociliary function and dysfunction of this system is an important risk factor for otitis media. The secreted antimicrobial molecules of the tubotympanum include lysozyme, lactoferrin, beta defensins, and the surfactant proteins A and D (SP-A, SP-D). Defects in the expression or regulation of these molecules may also be the major risk factor for otitis media.

Animals↗
PubMed2000

Human beta defensin is absent in burn blister fluid.

Defensins are a family of cationic antimicrobial peptides that participate in innate host defence. Human beta defensin-2 (HBD-2) is produced by human keratinocytes, and has a potent bactericidal activity against a wide spectrum of microorganisms. We have recently shown that expression of HBD-2 is present in normal skin and lost in the full-thickness burn wound. Defensins have been found in the blister fluid of chronic wounds. Our study was designed to examine blister fluid from partial-thickness burns for defensin content. Fluid from five patients was collected from partial-thickness burn blisters, and then analysed by sandwich Enzyme-Linked Immunosorbent Assay (ELISA) with a monoclonal antibody and rabbit polyclonal antibody to HBD-2. The assay was validated against a Western blot assay for HBD-2 in samples of bronchoalveolar lavage fluid from patients with inflammatory lung disease. No HBD-2 was detectable in any of the burn blister fluids analysed. HBD-2 is lost in the full-thickness burn wound, and we have now demonstrated its absence in burn blister fluid. This finding represents evidence of a host defence defect within the burn wound and suggests a possible therapeutic role for antimicrobial peptides in the management of burn wounds.

Adolescent↗
PubMed1999

Epithelial defensins impair adenoviral infection: implication for adenovirus-mediated gene therapy.

Epithelial cells have been to participate actively in host defense by producing small cationic peptides called defensins. To investigate the biological activity of epithelial defensins in more detail, we expressed two defensins, hBD-1 and HD-5, in eukaryotic cell lines. Defensins were localized in the cytoplasm and in cell culture medium and exhibited strong microbicidal activity toward Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Moreover, our data indicate that the presence of defensins protected the cells from adenoviral infection. The presence of HD-5 or hBD-1 reduced the infectivity of Av1CF2 three- to fivefold. These results imply that defensins must be considered a serious obstacle whenever adenovirus is used to deliver genes to epithelial cells.

Adenoviridae↗
PubMed1991

A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors.

The amino acid sequence of a major human epididymis-specific protein was deduced from the nucleotide sequence of its cloned cDNA. The encoded product showed characteristics of a secretory protein, with a signal peptide followed by a small (approximately 10-kDa), acidic (pI 4.3), and cysteine-rich polypeptide. The positions of half-cysteines suggested that it was a two-domain member of the family of 'four-disulfide core' proteins to which a number of proteinase inhibitors belong. Southern blot analyses of human genomic DNA showed that the transcripts originated from a single copy gene. Northern blot and in situ transcript hybridization specifically localized the HE4 (human epididymis gene product) mRNA to the epithelial cells of the epididymal duct, predominantly within the distal sections. A possible function in sperm maturation as indicated by amino acid similarities to extracellular proteinase inhibitors of genital tract mucous secretions is discussed in the context of its tissue-specific transcription.

Aged↗
PubMed2000

Effect of ions on antibacterial activity of human beta defensin 2.

Human beta defensin 2 (HBD-2), the most recently discovered human defensin, has been considered to work as a host defense substance against microbial infection. Using Escherichia coli ATCC 25922, we investigated how some cations and anions influenced the antimicrobial activity of HBD-2. This activity, measured in 10 mM phosphate buffer at a concentration of 20 microg/ml, reduced significantly in the presence of 100 and 150 mM sodium or potassium chloride. The reduction was not significantly different when the total amounts of sodium and potassium ions were equal. The kind and the valence of anions (chlorine and sulfate ions) did not affect the bactericidal activity as long as the concentrations of sodium ions were equal. Divalent ions (calcium and magnesium ions) added to 10 mM of Tris buffer significantly inactivated HBD-2 at much lower concentrations (more than or equal to 0.01 mM and 0.05 mM, respectively) than the monovalent ions did. These findings suggest that HBD-2 kills the bacteria through at least two phases, which are affected independently by either monovalent or divalent ions and unaffected by anions.

Anti-Bacterial Agents↗
PubMed1993

Tissue-specific gene expression as an indicator of epididymis-specific functional status in the boar, bull and stallion.

cDNA probes derived from genes expressed specifically in the human epididymis were used to examine gene expression in the epididymides of boar, bull and stallion by Northern hybridization. Two probes for the HE1 and HE4 gene products were found to recognize tissue-specific transcripts in all three species, with a regionally differential distribution within the epididymis. Additionally, antibodies recognizing the HE4 protein were shown to react specifically in the epididymis of the boar and bull. An extensive study of the boar showed that, whereas mRNA for the HE1-homologue was up-regulated markedly only at puberty, the HE4-homologue was already present at moderate levels prepubertally. The distribution of the HE1-homologue changed at sexual maturity from a maximum in the cauda epididymis in the 3-4-week-old pig, to a maximum in the corpus/caput region in the adult, while the shift was in the opposite direction for the HE4-homologue. Evidently, gene expression is not fixed regionally through epididymal development in this species. The abdominal epididymis of a hemicryptorchid pig also showed a differential change in expression for the two gene products by comparison with the scrotal testis from the same animal. The results suggest that the HE1 and HE4 gene homologues may be sensitive markers for physiological changes within the mammalian epididymis, and that the boar could prove a useful model to examine the regulation of these human epididymal transcripts.

Animals↗
PubMedDate not supplied

Function of human epididymal proteins in sperm maturation.

Human post-testicular proteins were cloned by subtractive screening of epididymal cDNA libraries, employing testis as the primary negative control. This method identified six human epididymal cDNAs, named HE1-HE6, which are derived from abundant epididymal mRNAs. With the exception of HE5, which turned out to be identical to the lymphocyte surface antigen CD52, they represented completely novel human gene products. To date, there is little information on their function and the mechanism of their deposition on the sperm surface. Unlike the sperm coating antigens, CD52 binds firmly to the sperm membrane via its GPI anchor during epididymal passage. Its synthesis is carefully regulated by the epididymal epithelium. From the results of both in vivo and in vitro studies it was concluded that androgen and temperature are principal factors synergistically modulating epididymal CD52 expression. The human counterparts of two well-known major rodent epididymal proteins, secretory epididymal glutathione peroxidase (sGPX) and acidic epididymal glycoprotein (AEG = Protein DE), were not cloned by the subtractive screening approach, but by RT-PCR amplification.

Antigens, CD↗
PubMed1994

Killing of Giardia lamblia by cryptdins and cationic neutrophil peptides.

Antimicrobial polypeptides such as the defensins kill a wide range of organisms, including bacteria, fungi, viruses, and tumor cells. Because of the recent finding that intestinal defensins, also known as cryptdins, are synthesized by the Paneth cells of the small intestinal crypts and released into the lumen, we asked whether defensins and other small cationic antimicrobial peptides could kill the trophozoites of Giardia lamblia, which colonize the small intestine. Four mouse cryptdins, two neutrophil defensins (HNP-1 [human] and NP-2 [rabbit]), and the unique tryptophan-rich bovine neutrophil polypeptide indolicidin each had some antigiardial activity against trophozoites in vitro. Cryptdins 2 and 3, indolicidin, and NP-2 each reduced viability by more than 3 log units in 2 h, and killing by all peptides was dose and time dependent. Exposure of trophozoites to peptides frequently resulted in cell aggregation and dramatic changes in morphology. The mechanism of binding and lysis appeared to involve charge interactions, since 150 mM NaCl as well as millimolar levels of Ca2+ and Mg2+ inhibited killing by most of the peptides. Our studies show that G. lamblia is sensitive to defensins and indolicidin and suggest that these small polypeptides could play a role in nonimmune host defenses.

Amino Acid Sequence↗
PubMed1998

Antibacterial peptides in bronchoalveolar lavage fluid.

Defensins and other antimicrobial peptides act in the innate host defense of epithelial surfaces. Human beta defensin 1 (hBD-1) has recently been shown to be expressed in airway epithelial cells and so has been implicated as a primary component of antibacterial activity in human lung. We attempted to purify these molecules from bronchoalveolar lavage fluid (BALF). Extraction of BALF on SepPak C-18 cartridges, followed by continuous acid-urea polyacrylamide gel electrophoresis and reverse-phase high-performance liquid chromatography yielded one fraction with antibacterial activity associated with factors of < 6.5 kD. N-terminal amino acid sequencing identified these peptides as human neutrophil defensins (HD) 1 through 3. No hBD-1 was detected. Together with lysozyme, it appears that HD-1 through -3 are the most prominent antimicrobial factors in BALF. The contribution of epithelial defensins such as hBD-1 to antibacterial defense of human airway in vivo remains to be elucidated.

Anti-Bacterial Agents↗