Neurotoxicity of human eosinophils

Durack, David T.; Sumi, S. M.; Klebanoff, Seymour J.

doi:10.1073/pnas.76.3.1443

Cited by 185 publications

(77 citation statements)

References 20 publications

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“…Although we cannot know for certain how many different cluster ribonucleases are expressed in this tissue, the lung is an interesting location for rR ribonucleases in general, given our recent findings regarding the function of the human ortholog, hEDN. Until recently, hEDN's physiologic function was a complete mystery; its name was derived from its nonphysiologic toxicity to rabbit Purkinje cells (Durack et al 1979(Durack et al , 1981. As part of our ongoing quest to determine a physiologic, ribonucleasedependent function for this protein, we have begun to explore the relationships linking human EDN's primary host cell-the human eosinophilic leukocyte-to diseases caused by the ssRNA respiratory viral pathogen RSV Kimpen et al 1992Kimpen et al , 1996Harrison et al 1999).…”

Section: Figmentioning

confidence: 99%

Rapid Evolution of the Ribonuclease A Superfamily: Adaptive Expansion of Independent Gene Clusters in Rats and Mice

et al. 1999

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Abstract. The two eosinophil ribonucleases, eosinophil-derived neurotoxin (EDN/RNase 2) and eosinophil cationic protein (ECP/RNase 3), are among the most rapidly evolving coding sequences known among primates. The eight mouse genes identified as orthologs of EDN and ECP form a highly divergent, species-limited cluster. We present here the rat ribonuclease cluster, a group of eight distinct ribonuclease A superfamily genes that are more closely related to one another than they are to their murine counterparts. The existence of independent gene clusters suggests that numerous duplications and diversification events have occurred at these loci recently, sometime after the divergence of these two rodent species (∼10-15 million years ago). Nonsynonymous substitutions per site (d N ) calculated for the 64 mouse/rat gene pairs indicate that these ribonucleases are incorporating nonsilent mutations at accelerated rates, and comparisons of nonsynonymous to synonymous substitution (d N / d S ) suggest that diversity in the mouse ribonuclease cluster is promoted by positive (Darwinian) selection. Although the pressures promoting similar but clearly independent styles of rapid diversification among these primate and rodent genes remain uncertain, our recent findings regarding the function of human EDN suggest a role for these ribonucleases in antiviral host defense.

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Section: Figmentioning

confidence: 99%

Rapid Evolution of the Ribonuclease A Superfamily: Adaptive Expansion of Independent Gene Clusters in Rats and Mice

et al. 1999

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“…Durack et al 22 described a syndrome of stiffness and ataxia, progressing to severe paralysis in rabbits after intrathecal injection of eosinophil-derived neurotoxin. Histopathologic examination of the central nervous system from these animals revealed diffuse spongiform demyelination, most prominent in the cerebellum, brainstem, and spinal cord.…”

Section: Discussionmentioning

confidence: 99%

“…More recent investigations have shown that the occurrence of the Gordon phenomenon depends on the presence of eosinophils in the tissue from which suspensions are derived. 22 A specific causative agent, eosinophil-derived neurotoxin, was eventually isolated and purified in 1981. 23 Experimental animals suffering manifestations of the Gordon phenomenon, such as paralysis or ataxia, are usually killed; animals with mild or moderate reactions may recover essentially all of their normal abilities.…”

Section: Discussionmentioning

confidence: 99%

Eosinophil-Associated Inflammation and Elaboration of Eosinophil-Derived Proteins in 2 Children With Raccoon Roundworm (Baylisascaris procyonis)Encephalitis

Moertel

Kazacos

Butterfield³

et al. 2001

Pediatrics

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ABSTRACT. Objective. Eosinophil-associated proteins, especially eosinophil-derived neurotoxin, may be important contributors to the neurologic pathology and symptoms caused by Baylisascaris procyonis infection.Methods. Two cases of severe B procyonis encephalitis with evidence of marked eosinophil degranulation in the central nervous system are presented. Serial cerebrospinal fluid (CSF) specimens were collected from each patient during the course of their illness. Antibodies against B procyonis were measured in the patients' serum and CSF. Levels of the eosinophilopoietin interleukin-5 (IL-5) and 2 important eosinophil proteins, eosinophilderived neurotoxin and major basic protein, were assayed in the CSF.Results. Both patients had rapidly progressive central nervous system disease with evidence of eosinophilic meningoencephalitis. Both tested positive for antibodies to B procyonis in serum and CSF and had progressively worsening deep white matter changes on magnetic resonance images of the brain. CSF levels of IL-5, eosinophilderived neurotoxin, and major basic protein were markedly elevated over controls.Conclusions. This is the first report of the measurement of IL-5, eosinophil-derived neurotoxin, and major basic protein in human CSF. In addition to traumatic damage and necrosis caused by migrating larvae, eosinophil-derived neurotoxin from associated eosinophilic inflammation may be an important contributory factor in the pathogenesis of B procyonis encephalitis. Pediatrics 2001;108(5). URL: http://www.pediatrics.org/cgi/content/ full/108/5/e93; parasite, eosinophil-derived-neurotoxin, major basic protein, eosinophilia, hypereosinophilia, interleukin-5, encephalitis, child.ABBREVIATIONS. CSF, cerebrospinal fluid; CNS, central nervous system; MRI, magnetic resonance imaging; IL-5, interleukin-5; PBS, phosphate-buffered saline.B aylisascaris procyonis, the common raccoon ascarid, is a well-known cause of severe neurologic disease (neural larva migrans) in animals, with cases identified in Ͼ90 species of mammals and birds in North America. 1,2 Neural larva migrans and eosinophilic meningoencephalitis attributable to B procyonis have now been identified in 7 young children, including the 2 reported here. [3][4][5][6][7] We specifically note a novel correlation with elevated cerebrospinal fluid (CSF) levels of major basic protein and the neurotoxic protein eosinophil-derived neurotoxin associated with eosinophilic inflammation in these 2 cases. We hypothesize that the severe neurologic consequences of Baylisascaris encephalitis are attributable, in part, to marked eosinophil degranulation and release of these toxic eosinophil proteins in the central nervous system (CNS) of patients with this disease. CASE REPORTS Case 1A 13-month-old boy became irritable 3 weeks before hospital admission, then became progressively irritable, ataxic, and weak. Three days before admission, he was unable to cruise, sit up, or walk, and exhibited dysmetria. He then had an episode of limb twitching followed by rigidity and decreased...

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“…Experimental support for this concept comes from studies where purified eosinophil suspensions were injected intracisternally into rabbits and found to produce forelimb stiffness and ataxia within a few days. The eosinophil extracts caused marked tissue damage, with loss of Purkinje cells and spongiform vacuolation in the white matter of the spinal cord and the cerebellar Purkinje cell layer (14). Normal blood eosinophils do not show immunoreactivity with antibody EG2, which reacts with ECP (3).…”

Section: Case Reportmentioning

confidence: 99%

Spontaneous Remission of a Massive CNS Inflammation with Eosinophilic Infiltrate

et al. 2003

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Neurotoxicity of human eosinophils

Cited by 185 publications

References 20 publications

Rapid Evolution of the Ribonuclease A Superfamily: Adaptive Expansion of Independent Gene Clusters in Rats and Mice

Rapid Evolution of the Ribonuclease A Superfamily: Adaptive Expansion of Independent Gene Clusters in Rats and Mice

Eosinophil-Associated Inflammation and Elaboration of Eosinophil-Derived Proteins in 2 Children With Raccoon Roundworm (Baylisascaris procyonis)Encephalitis

Spontaneous Remission of a Massive CNS Inflammation with Eosinophilic Infiltrate

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