Disease relevance of DEFA3

• Temperature shift experiments indicated that retrocyclin 2 and human alpha defensins human neutrophil peptide 1 (HNP 1) to HNP 3 protected human cells from HSV-2 by different mechanisms [1].
• The bactericidal activities of purified defensins HNP-1 and HNP-2 were equal, and both of these activities were greater than HNP-3 activity against strains of Capnocytophaga sputigena and Capnocytophaga gingivalis [2].
• In contrast, their relative potencies against E. coli and E. aerogenes were HNP4 > HNP2 > HNP1 = HNP3 [3].
• Identification of HNP3 as a tumour marker in CD4+ and CD4- lymphocytes of patients with cutaneous T-cell lymphoma [4].
• However, the HNP-3 content was significantly reduced in neutrophils from patients with generalized early-onset periodontitis [5].

High impact information on DEFA3

• Using the most stringent statistical analysis (Bonferroni correction), 15 genes were found highly up-regulated in SLE patients, 14 of which are targets of IFN and one, defensin DEFA-3, a major product of immature granulocytes [6].
• Purified preparations of each of the three human defensins (HNP-1, HNP-2, HNP-3) were then tested [7].
• Three defensins (human neutrophil peptide defensin [HNP]-1, HNP-2, and HNP-3) constitute between 30 and 50% of the total protein in azurophil granules of human PMN [8].
• We investigated the regulation of HNP-1 and HNP-3 expression at the transcriptional level using a promyelocytic HL-60 cell line [9].
• 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 [10].

Chemical compound and disease context of DEFA3

• Neutrophils from 10 patients with early-onset periodontitis and 8 healthy control subjects were assessed for elastase isozymes 1 through 4, cathepsin G isozymes 1 through 4 and defensins (HNP-1, HNP-2 and HNP-3) using cationic and acid urea polyacrylamide gel electrophoresis [5].

Biological context of DEFA3

• Inter-population variability of DEFA3 gene absence: correlation with haplotype structure and population variability [11].
• Association analysis of DEFA3 absence with 136 SNPs from a 100-kb region identified a conserved haplotype in the Caucasian population, extending for the whole region [11].
• The alpha-defensin cluster on human chromosome 8p23.1 is one of the better-characterized CNVs, in which high copy number variability affecting the DEFA1 and DEFA3 genes has been reported [11].
• Although the primary amino acid sequences of HNP-1, 2, and 3 are identical except for a single amino-terminal amino acid alteration, HNP-1 and HNP-2 killed C. albicans but HNP-3 did not [12].
• The results of the study suggest that human alpha-defensins HNP-1, HNP-2, and HNP-3 are up-regulated after surgery, and may in addition to their antimicrobial properties have an important role in wound healing [13].

Anatomical context of DEFA3

• Inheritance of unequal numbers of the genes encoding the human neutrophil defensins HP-1 and HP-3 [10].
• Purified defensins HNP-1 and HNP-2 (kindly provided by Dr. R. I. Lehrer, UCLA) were also potent chemoattractants for human T-cells, while HNP-3 was inactive [14].
• Human defensin HNP-1 and the closely related HNP-3 are amphiphilic dimers that act in part by permeabilizing cell membranes [15].
• Four monoclonal antibodies (HP-1, HP-2, HP-3 and HP-4) with differing reactivities were raised against human synovial fluid phospholipase A2 [16].

Associations of DEFA3 with chemical compounds

• The peptides, HNP-1, HNP-2, and HNP-3, which we have termed defensins, were rich in cystine, arginine, and aromatic residues, but were devoid of free sulfhydryl groups and carbohydrate moieties [17].
• The first peak was resolved further by C4 reversed phase HPLC and yielded an active fraction shown by NH2-terminal amino acid sequence analysis to contain defensins HNP-1, HNP-2, and HNP-3 [14].
• Bilirubin UGTs (HP2 and HP3) were not detectable in the kidney and HP3 was the major isoform in the liver [18].

Analytical, diagnostic and therapeutic context of DEFA3

• MEASUREMENTS AND RESULTS: Concentrations of alpha-defensins (human neutrophil peptide [HNP]-1, HNP-2, and HNP-3) were measured by radioimmunoassay in plasma and BAL fluid (BALF) [19].
• Using ultrafiltration to remove the high molecular weight toxin and enzymes followed by reverse-phase HPLC, three bioactive tridecapeptides, designated "HP-1, HP-2 and HP-3" were isolated from the venom [20].

References