Disease relevance of RNASE3

• Eosinophil cationic protein (ECP) is located in the matrix of the eosinophil's large specific granule and has marked toxicity for a variety of helminth parasites, hemoflagellates, bacteria, single-stranded RNA virus, and mammalian cells and tissues [1].
• By utilizing the colloidal gold particle technique, we localized eosinophil granule major basic protein, eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN) in human nasal polyp sections by immunoelectron microscopy [2].
• CONCLUSIONS: ECP contributes to surfactant dysfunction in asthma, which in turn could lead to airway obstruction [3].
• ECP concentration in milk was under the detection limit (2 microg/L) in all the mothers with a healthy infant, whereas detectable levels were found in 27% of mothers with a CMA infant and in 42% of those with a baby with atopic dermatitis [4].
• This is the first demonstration that some eosinophil cationic proteins, namely ECP and MBP, found at the site of heart damage in patients with eosinophilia, act as complete secretagogues on HHMC [5].

High impact information on RNASE3

• The EDN/ECP gene pair arose from a recent duplication event that occurred after the divergence of New World and Old World monkeys [6].
• We have traced the rapid molecular evolution of eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP), two host defense proteins that are members of the mammalian ribonuclease gene family [6].
• One of the major granule proteins of human eosinophils is the eosinophil cationic protein (ECP) which has been shown to damage schistosomula of Schistosoma mansoni at concentrations as low as 10(-7) [7].
• No ECP mRNA was detected in uninduced HL-60 cells, or in HL-60 cells induced toward monocytic differentiation with vitamin D3 or toward neutrophilic differentiation with DMSO [8].
• The open reading frame encodes a previously unidentified 27-amino acid leader sequence preceding a 133-residue mature ECP polypeptide with a molecular mass of 15.6 kD [8].

Chemical compound and disease context of RNASE3

• Eosinophil cationic protein (ECP), tryptase, and total and specific IgE for inhalant allergens and Staphylococcus aureus enterotoxins were measured (ImmunoCAP) [9].
• 2. Eosinophil and eosinophil products, such as ECP, are also increased in tears of VKC patients and, in hay fever conjunctivitis, accumulate during the late-phase of allergic reaction following specific allergen challenge [10].
• Before steroid treatment, patients with atopic dermatitis demonstrated significantly higher serum levels of sIL-2R, ICAM-1, and ECP than healthy controls (P < 0.001), whereas ELAM-1 levels were not different between the groups [11].
• Two proton ionophores (DNP and carbonyl cyanide m-chlorophenyl hydrazone) protected E. coli from the bactericidal effects of ECP but not from MBP [12].
• Gliadin, administered by perfusion to the jejunal segment, induced a fourfold increase in ECP secretion and a twofold increase of histamine secretion in patients with celiac disease (n = 7), but did not influence the secretion rates of these substances in healthy controls (n = 3) [13].

Biological context of RNASE3

• ECP is a small, basic protein found in the matrix of the eosinophil's large specific granule that has cytotoxic, helminthotoxic, and ribonuclease activity, and is a member of the ribonuclease multigene family [8].
• Amino acid sequence analyses showed that ECP-1 and ECP-2 are identical from residue 1 through residue 59 and that the sequences of EDN and ECP are highly homologous (37 of 55 residues identical) [14].
• PD98 059 and SB202 190 both caused inhibition of eotaxin-induced ECP release and chemotaxis [15].
• The ECP nucleotide sequence shows similarity to EDN, rat pancreatic ribonuclease, and human angiogenin; all are members of the ribonuclease gene superfamily [16].
• Here we present evidence demonstrating that the gene encoding ECP is regulated in an analogous fashion and that an intronic enhancer element functioning in both genes is a consensus binding sequence for the transcription factor NFAT-1 [17].

Anatomical context of RNASE3

• We have isolated a 725-bp full-length cDNA clone for the human eosinophil cationic protein (ECP) [8].
• The eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are both small, cationic ribonuclease toxins that are stored in and secreted by activated human eosinophilic leukocytes [17].
• The high concentration of positive charges and the particular orientation of the side-chains of these residues may also be related to the low activity of ECP as a ribonuclease and provides an explanation for its unique cytotoxic role through cell membrane disruption [18].
• We tested whether EDN and ECP are present in mature neutrophils [19].
• ECP concentration in human milk was measured by commercial UniCAP method [4].

Associations of RNASE3 with chemical compounds

• Both ECP and EDN possess neurotoxic and ribonuclease activities [16].
• In addition, degranulation of ECP in response to Ca(2+) ionophore, immobilized IgG and serum from allergic patients was inhibited by SP-D [20].
• Restimulation with the same agonist (PAF or C5a) was unsuccessful as assessed by monitoring intracellular calcium concentration and ECP release [21].
• ECP levels after allergen challenge correlate well to surfactant dysfunction [3].
• Suplatast tosilate (IPD-1151T), a new anti-allergic agent, has shown beneficial effect in the treatment of asthma, associated with reduced bronchoalveolar lavage eosinophil infiltration and eosinophilic cationic protein (ECP) release in serum and sputum [22].
• Analysis of ECP mt1 (R34A/W35A/R36A/K38A) showed that these charged and aromatic residues were involved in ECP binding to heparin and the cell surface [23].

Other interactions of RNASE3

• Radioimmunoassay, using monoclonal antibodies, of fractions from the heparin-Sepharose chromatography showed one peak of EDN activity and two peaks of ECP activity (termed ECP-1 and ECP-2) [14].
• Eosinophil cationic protein (ECP) is one of two RNase A-superfamily ribonucleases found in secretory granules of human eosinophilic leukocytes [24].
• Activation by sIgA and CD28 ligation resulted in the release of ECP and EDN, which was inhibited by IPD-1151T [22].
• In a model of eosinophil degranulation, we show that eosinophils release ECP upon short-term GM-CSF priming and stimulation with either platelet-activating factor (PAF) or the anaphylatoxin C5a, but not eotaxin [21].
• Such eosinophils did not increase cellular ECP levels even in the presence of the eosinophil survival factor GM-CSF in overnight cultures [21].

Analytical, diagnostic and therapeutic context of RNASE3

• Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) were isolated from lysates of human eosinophil granules by gel filtration and ion exchange chromatography on heparin-Sepharose [14].
• OBJECTIVE: Because the potential role of ECP in the inhibition of surfactant function is not known, we tested the hypothesis of whether ECP levels in bronchoalveolar lavage fluid (BALF) of patients with asthma after segmental allergen provocation correlate to surfactant dysfunction [3].
• By indirect immunofluorescence, both eosinophils and neutrophils stained with antibodies to EDN and ECP [19].
• The release of ECP and eosinophil derived neurotoxin (EDN) was measured by radioimmunoassay and cytokine production was determined by ELISA following activation with sIgA or anti-CD28 [22].
• The 434 genotype in the ECP-gene was detected by cleavage of the amplified DNA sequence with the restriction enzyme PstI and analysis of the cleaved product by agarose gel electrophoresis [25].

References