Assignment of defensin gene(s) to human chromosome 8p23

Sparkes, Robert S.; Kronenberg, Mitchell; Heinzmann, C.; Daher, Kathleen A.; Klisak, Ivana; Ganz, Tomas; Mohandas, T.

doi:10.1016/0888-7543(89)90052-9

Cited by 78 publications

(29 citation statements)

References 18 publications

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“…To confirm the results obtained by using the HNP mixture purified from patients with cystic fibrosis, experiments were repeated using commercially available synthetic HNP-1 and A549 cells because HNP-1 is the most abundant isoform among HNPs that include HNP-1, HNP-2, and HNP-3 in granule content in neutrophils 36,37,39,40 and in the purified HNP mixture used. A similar inhibition of the HNP-1-induced IL-8 production was reproduced by the use of P2Y 6 antisense oligonucleotide, but the cells showed much less IL-8 release in response to the commercially synthesized HNP-1 than to the purified HNP mixture ( Figure 6E).…”

Section: P2y 6 Signaling Regulates Hnp-induced Il-8 Productionmentioning

confidence: 99%

Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway

Khine

Sorbo

Vaschetto

et al. 2006

Blood

105

106

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Section: P2y 6 Signaling Regulates Hnp-induced Il-8 Productionmentioning

confidence: 99%

Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway

Khine

Sorbo

Vaschetto

et al. 2006

Blood

105

106

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“…They lack enzymatic activity, and like the serine proteinases, are produced during neutrophil development as preprodefensins [58,59]. The neutrophil defensin gene for HNP-1 has been mapped to chromosome 8p23 [60]. Mature defensins are stored in a dense subset of azurophilic granules that contains no or little elastase and myeloperoxidase [61], and constitute 30-50% of the total protein content of the azurophilic granules ( fig.…”

Section: Defensinsmentioning

confidence: 99%

Neutrophil serine proteinases and defensins in chronic obstructive pulmonary disease: effects on pulmonary epithelium

Hiemstra

Wetering²,

Stolk³

1998

Eur Respir J

127

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Neutrophils have the capacity to accumulate in high numbers in the lung during infection and inflammation. Because they play an important role in host defence against infection, but may also cause tissue injury, these cells are thought to be involved in the pathogenesis of various inflammatory lung disorders, including chronic bronchitis and chronic obstructive pulmonary disease. Neutrophil products that may mediate tissue injury at sites of neutrophil-dominated inflammation include the neutrophil serine proteinases elastase, cathepsin G and proteinase 3, and the nonenzymatic defensins. One of the targets of the neutrophil is the lung epithelium, and in vitro studies have revealed that both the serine proteinases and neutrophil defensins markedly affect the integrity of the epithelial layer, decrease the frequency of ciliary beat, increase the secretion of mucus, and induce the synthesis of epithelium-derived mediators that may influence the amplification and resolution of neutrophil-dominated inflammation. Both neutrophil elastase and defensins induce the release of the neutrophil chemoattractant chemokine interleukin-8 from respiratory epithelial cells. The alpha1-proteinase inhibitor (alpha1-PI) is a well-characterized inhibitor of neutrophil elastase, that also blocks the cytotoxic and stimulatory activity of defensins towards epithelial cells. The elastase inhibitory activity of alpha1-PI is also abrogated by the binding of defensins to this inhibitor. Incubation of epithelial cells with neutrophil defensins in combination with either elastase or cathepsin G resulted in decreased effects on the epithelial cells compared with those observed when the cells were incubated with defensins, elastase or cathepsin G separately. These results suggest that neutrophil defensins and serine proteinases cause injury and stimulate epithelial cells to produce chemokines that attract more neutrophils to the site of inflammation. The effects of neutrophil defensins and serine proteinases on epithelial cells appear to be restricted by proteinase inhibitors and by inhibitory interactions between these sets of neutrophil granule proteins.

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“…Unequal Numbers of HP-1/3-like Genes-The genes encoding the neutrophil defensins have been mapped to human chromosome 8 (31,44). Therefore, to help determine the source of the variation in this gene family, we obtained multiple DNA samples from somatic cell hybrids that were prepared using cells from a single individual and that contained either one or both copies of chromosome 8 (45).…”

Section: Figmentioning

confidence: 99%

Inheritance of Unequal Numbers of the Genes Encoding the Human Neutrophil Defensins HP-1 and HP-3

Mars

Patmasiriwat

Maity

et al. 1995

Journal of Biological Chemistry

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It is unclear whether the six known human defensin peptides are all encoded by separate genes or whether some of them are allelic. Three of the peptides, HP-1, HP-2, and HP-3, differ by only one amino acid, and it is thought that HP-2 may represent a proteolytic product of HP-1 and/or HP-3. To help determine the relationship of these three proteins, we isolated a nearly full-length cDNA encoding HP-1 with a sequence very similar to, but different from, the previously isolated HP-1 and -3 cDNAs. Gene copy number experiments established that there were at least two but fewer than five defensin genes with a high level of similarity to the HP-1 cDNA (HP-1/3-like). Three genomic clones were isolated that contained two different configurations of the HP-1/3-like sequences. Sequencing established that one encoded the HP-1 peptide, whereas the other encoded HP-3. Analysis of DNAs obtained from 18 unrelated individuals by Southern blot analysis revealed the expected fragments as well as additional fragments that were not present in the genomic clones. This suggested the possibility of alleles; however, when DNAs from families were examined, these fragments did not segregate in an obvious Mendelian fashion. The HP-1/3-like defensin genes are on human chromosome 8. Surprisingly, somatic cell hybrid mapping showed that the number of HP-1/3-like genes on isolated copies of chromosome 8 was variable. We conclude that individuals can inherit versions of chromosome 8 harboring either two or three copies of the genes that encode the HP-1, HP-2, and/or HP-3 peptides.Corticostatins, defensins, and cryptdins are members of an unusual family of peptides that have been isolated from the alveolar macrophages, neutrophils, bone marrow leukocytes, and/or intestinal Paneth cells of rabbits, guinea pigs, mice, rats, and/or humans (1-13). These proteins are small, often cationic peptides (29 -35 amino acids) with a characteristic cysteine-rich structure and were originally isolated because of their anti-adrenocorticotrophin hormone (corticostatic) (6, 7) or antimicrobial (defensin) activities (1-4). Subsequently, sequence analysis of a cDNA clone revealed that cryptdin, from mouse intestinal Paneth cells, is a family member (13). Recently, Paneth cell sequences of human origin have also been identified (14,15). Presently, the family consists of six human, six rabbit, seven rat, two guinea pig, and six mouse sequences.

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Assignment of defensin gene(s) to human chromosome 8p23

Cited by 78 publications

References 18 publications

Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway

Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway

Neutrophil serine proteinases and defensins in chronic obstructive pulmonary disease: effects on pulmonary epithelium

Inheritance of Unequal Numbers of the Genes Encoding the Human Neutrophil Defensins HP-1 and HP-3

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