Ribonuclease is partly responsible for the HIV-1 inhibitory effect activated by HLA alloantigen recognition

Rugeles, Marı́a Teresa; Trubey, Charles M.; Bedoya, Victoria I; Pinto, Lígia A.; Oppenheim, Joost J.; Rybak, Susanna M.; Shearer, Gene M.

doi:10.1097/00002030-200303070-00002

Cited by 87 publications

(84 citation statements)

References 17 publications

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“…8B) demonstrated that upon treatment by a combination of TNF-␣ and LPS for 2 h, macrophage began to secrete EDN into the culture supernatant, which peaked at 8 h. The EDN protein appeared as two bands of ϳ31 and 37 kDa, which were larger than the size of rEDN (17.5 kDa, without glycosylation). The appearance of two bands larger than the rEDN was due presumably to differential glycosylation of EDN because, using the same polyclonal antiserum, Rugeles et al (25) also found that EDN generated by cultured human PBMC appears on a SDS-PAGE gel as bands of 31-40 kDa. Therefore, EDN expression by macrophages can be rapidly induced.…”

Section: Edn Expression By Macrophages Is Induciblementioning

confidence: 98%

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Human Ribonuclease A Superfamily Members, Eosinophil-Derived Neurotoxin and Pancreatic Ribonuclease, Induce Dendritic Cell Maturation and Activation

Yang

Chen

Rosenberg

et al. 2004

The Journal of Immunology

139

128

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A number of mammalian antimicrobial proteins produced by neutrophils and cells of epithelial origin have chemotactic and activating effects on host cells, including cells of the immune system. Eosinophil granules contain an antimicrobial protein known as eosinophil-derived neurotoxin (EDN), which belongs to the RNase A superfamily. EDN has antiviral and chemotactic activities in vitro. In this study, we show that EDN, and to a lesser extent human pancreatic RNase (hPR), another RNase A superfamily member, activates human dendritic cells (DCs), leading to the production of a variety of inflammatory cytokines, chemokines, growth factors, and soluble receptors. Human angiogenin, a RNase evolutionarily more distant to EDN and hPR, did not display such activating effects. Additionally, EDN and hPR also induced phenotypic and functional maturation DCs. These RNases were as efficacious as TNF-␣, but induced a different set of cytokine mediators. Furthermore, EDN production by human macrophages could be induced by proinflammatory stimuli. The results reveal the DC-activating activity of EDN and hPR and suggest that they are likely participants of inflammatory and immune responses. A number of endogenous mediators in addition to EDN have been reported to have both chemotactic and activating effects on APCs, and can thus amplify innate and Ag-specific immune responses to danger signals. We therefore propose these mediators be considered as endogenous multifunctional immune alarmins.

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Section: Edn Expression By Macrophages Is Induciblementioning

confidence: 98%

“…In addition, EDN has also been shown to be responsible in part for the anti-HIV-1 activity found in the supernatant of MLCs (25).…”

mentioning

confidence: 99%

Human Ribonuclease A Superfamily Members, Eosinophil-Derived Neurotoxin and Pancreatic Ribonuclease, Induce Dendritic Cell Maturation and Activation

Yang

Chen

Rosenberg

et al. 2004

The Journal of Immunology

139

128

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“…90 Other factors, such as ribonucleases may also have antiviral activity. 91 Overall, anti-X4 viruses CAF has yet to be accounted for. The importance of these factors and others to be discovered is clear and it is straightforward to envision how through gene therapy one could endogenously express them in naturally nonproducing cells.…”

Section: Prospectsmentioning

confidence: 99%

Gene therapy progress and prospects: Novel gene therapy approaches for AIDS

Wolkowicz

Nolan

2005

Gene Ther

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“…Furthermore, an exploration of complementary substitutions occurring during the evolution of EDN gene duplication at the divergence of the New World monkey lineages through the higher primates suggests that augmented ribonuclease activity and enhanced ribonuclease activity have developed coincidentally [35]. EDN also has activity against human immunodeficiency virus in vitro when tested in similar tissue-culture based assay systems [36][37][38]. Although the antiviral activity of the mouse eosinophil-associated ribonucleases has not been evaluated as clearly, eosinophils augment hRSV clearance in a mouse model, and can respond directly to hRSV by up-regulating mRNA encoding mouse eosinophil-associated RNases 1 and 2 [39].…”

Section: Edn Reduces Virus Infectivitymentioning

confidence: 99%

Eosinophil-Derived Neurotoxin / RNase 2: Connecting the Past, the Present and the Future

Rosenberg¹

2008

CPB

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The eosinophil-derived neurotoxin (EDN, also known as eosinophil protein-X) is best-known as one of the four major proteins found in the large specific granules of human eosinophilic leukocytes. Although it was named for its discovery and initial characterization as a neurotoxin, it is also expressed constitutively in human liver tissue and its expression can be induced in macrophages by proinflammatory stimuli. EDN and its divergent orthologs in rodents have ribonuclease activity, and are members of the extensive RNase A superfamily, although the relationship between the characterized physiologic functions and enzymatic activity remains poorly understood. Recent explorations into potential physiologic functions for EDN have provided us with some insights into its role in antiviral host defense, as a chemoattractant for human dendritic cells, and most recently, as an endogenous ligand for toll-like receptor (TLR)2.

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Ribonuclease is partly responsible for the HIV-1 inhibitory effect activated by HLA alloantigen recognition

Abstract: These findings indicate that the majority of the soluble HIV-1 inhibitory activity contained in the supernatants of mixed lymphocyte reactions is due to EDN or a closely related RNase.

Cited by 87 publications

References 17 publications

Human Ribonuclease A Superfamily Members, Eosinophil-Derived Neurotoxin and Pancreatic Ribonuclease, Induce Dendritic Cell Maturation and Activation

Human Ribonuclease A Superfamily Members, Eosinophil-Derived Neurotoxin and Pancreatic Ribonuclease, Induce Dendritic Cell Maturation and Activation

Gene therapy progress and prospects: Novel gene therapy approaches for AIDS

Eosinophil-Derived Neurotoxin / RNase 2: Connecting the Past, the Present and the Future

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