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PubMed1994

Nitrogen monoxide transport mechanisms.

The present article focuses on the possible existence of transport forms of nitrogen monoxide (NO) in biological tissues. Stimulated by the present controversy on the identity of L-arginine-derived endothelium-derived relaxing factor (EDRF) experiments were designed to clarify whether or not EDRF is a nitrosyl-iron complex. Synthetic dinitrosyl-iron-di-L-cysteine--(NO)2Fe(L-cysteine)2, a low molecular mass dinitrosyl-iron-dihiolate complex (DNIC)--exhibits similar pharmacological properties as EDRF. It is a potent (EC50 10 nmol/l) endothelium-independent, labile (< 2 min), superoxide radical-sensitive vasodilator and a direct activator of soluble guanylyl cyclase. In stimulated endothelial cells a paramagnetic DNIC associated with intracellular proteins was detected by electron spin resonance (ESR) spectroscopy. In the presence of N-acetyl-L-cysteine a low molecular mass DNIC released from endothelial cells was specifically trapped and detected in the extracellular medium as a paramagnetic albumin-DNIC. Due to release of DNIC the content of endothelial non-heme iron decreased after prolonged (1 h) agonist-induced stimulation in iron-free medium. Therefore, it is conceivable that endothelial NO forms high molecular (protein-bound) and low molecular DNIC. The protein-bound DNIC may serve as a reservoir for low molecular DNIC. The low molecular DNIC permeates the cell membrane and may thus act as an EDRF. The biological significance of DNIC may reside less in stabilization of free NO than in modulation of its reactivity. Thus, it is conceivable that DNIC reacts more selectively with proteins essential for NO-mediated signal transduction. By this mechanism signal transduction by NO will become more efficient and directed to certain pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Detection of free radicals as a consequence of dog tracheal epithelial cellular xenobiotic metabolism.

1. Spin-trapping techniques have been used to examine the metabolism of three xenobiotics known to produce free radicals during their metabolism. Reaction with oxygen generated superoxide, the location of which was dependent upon the xenobiotic. 2. Paraquat was metabolized by dog trachea epithelial cells under anaerobiosis to the paraquat free radical, some of which diffused into the extracellular milieu. With the addition of oxygen, superoxide was spin-trapped both intra- and extracellularly. 3. When menadione was metabolized by epithelial cells, superoxide was spin-trapped within the cell and in the surrounding media. However, in this case, extracellular superoxide arose as the result of the disproportionation reaction of menadione and menadiol, resulting from DT-diaphorase reduction of menadione followed by diffusion into extracellular space, to give the menadione semiquinone. Reduction of oxygen resulted in formation of superoxide. 4. For nitrazepam, only intracellular superoxide was generated, resulting from the one-electron reduction of this drug to its corresponding nitro anion free radical. Reaction with oxygen produced superoxide.

Animals↗

PubMed2002

In vivo molecular imaging.

The relatively young field of molecular imaging is focused on the visualization of molecular phenotypes in whole organisms. This is achieved using imaging systems based on radionuclides, nuclear magnetic resonance, ultrasound, or the visible-IR region of the optical spectrum. Molecularly defined contrast in these modalities is generated by exogenous probes of the endogenous proteome, or through transgenes. Examples of exogenous probes include those that are transported and trapped (glucose, nucleoside analogs), those directed against extracellular receptors (somatostatin, opioid, melanotropin), and those activated by extracellular proteases. Transgenes that have been used in molecular imaging include the above receptors, non-mammalian enzymes that trap pro-drugs (HSV-tk, yeast CD), and optical reporter proteins (luciferase, fluorescent proteins). Cutting edge technologies in this field include in vivo assays for protein-protein interactions, and in vivo assays for mRNA expression patterns. The number of degrees of freedom in designing new agents is daunting, and advancements in this field will require a significant participation from molecular and cellular biochemists.

Animals↗

PubMed1994

Role of Ca2+ in the vascular contraction caused by a thrombin receptor activating peptide.

Thrombin receptor activating peptide (TRAP) caused a slowly developing, sustained contraction of endothelium denuded rat aortic rings. Both nifedipine (10 microM) and removal of Ca2+ from the physiological salt solution (PSS) caused significant (60-75%) reductions in the contractile response to TRAP. In Ca(2+)-free PSS the response to both phenylephrine and TRAP were markedly reduced. Readministration of Ca2+ quickly restored the full response to phenylephrine. In contrast, readministration of Ca2+ only partially restored the TRAP response. Depletion of TRAP-sensitive intracellular Ca2+ stores had no effect on the phenylephrine response in Ca(2+)-free PSS. A threshold contracting concentration of TRAP (10 microM) enhanced contractions to the activator of voltage regulated Ca2+ channels Bay K 8644. Similarly, Bay K 8644 enhanced responses to TRAP. It is concluded that the contractile response of rat aortic rings to TRAP is largely mediated by influx of extracellular Ca2+. Furthermore, the intracellular Ca2+ pool(s) activated appears to be different from the phenylephrine-sensitive pools, which cannot be depleted by TRAP.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2000

Regulation of vascular smooth muscle cell proliferation by nuclear factor-kappaB and its inhibitor, I-kappaB.

Proliferation of vascular smooth muscle cells (SMC) is a crucial event in the formation of atherosclerotic tissues and is regulated by nuclear transcriptional factors including nuclear factor-kappaB (NF-kappaB). We constructed a reporter gene assay to measure NF-kappaB-dependent transcriptional activity in SMC. Thrombin receptor-activating peptide (TRAP) and basic fibroblast growth factor (bFGF) stimulated SMC proliferation and rapidly enhanced the NF-kappaB transcriptional activity in a dose-dependent manner. 4-Cyano-5,5-bis-(methoxyphenyl)4-pentenoic acid (E5510) significantly inhibited SMC proliferation and also suppressed NF-kappaB transcription stimulated by TRAP and bFGF. In contrast, although tumor necrosis factor (TNF)-alpha activated NF-kappaB transcription, E5510 had no effect on TNF-alpha-induced activation. NF-kappaB was activated after the stimulation of TRAP, bFGF, and TNF-alpha in electrophoretic mobility shift assay, and E5510 suppressed the NF-kappaB activation induced by TRAP and bFGF but not the activation by TNF-alpha. Western blot analysis of I-kappaBalpha and I-kappaBbeta, inhibitors of NF-kappaB, indicated that I-kappaBalpha degradation, rather than I-kappaBbeta degradation, was important in NF-kappaB activation after the stimulation of TRAP and bFGF. PD98059, an inhibitor of extracellular signal-regulated kinase (ERK) kinase, suppressed NF-kappaB transcriptional activity and SMC proliferation. The phosphorylation of ERK1/2 was rapidly induced by TRAP and bFGF but not by TNF-alpha. These results indicate that TRAP and bFGF induced I-kappaB degradation and NF-kappaB activation through a distinct pathway from TNF-alpha and that ERK1/2 may play an important role in NF-kappaB activation induced by TRAP and bFGF.

Animals↗

PubMed1995

Role of neutrophils in radical production during ischemia and reperfusion of the rat brain: effect of neutrophil depletion on extracellular ascorbyl radical formation.

A growing body of experimental data indicate that oxygen radicals may mediate the brain injury during ischemia-reperfusion. One potential source of oxygen radicals is activated neutrophils. To study the role of neutrophils in radical production during cerebral ischemia-reperfusion, we evaluated the effects of depletion of circulating neutrophils by administration of an anti-neutrophil monoclonal antibody (RP3) on radical formation in rats with 1-h middle cerebral artery (MCA) occlusion. In the present study, we employed a new electron spin resonance method coupled with brain microdialysis. The method uses the endogenous ascorbyl radical (AR) concentration as a marker of oxygen radicals and requires no spin-trapping agents. In the vehicle controls, extracellular AR decreased during MCA occlusion. After reperfusion, AR significantly increased at 30 min and 1 h, returned to near basal level until 2 h, and increased again at 24 h after reperfusion. In the rats treated with RP3, AR decreased during MCA occlusion to the same extent as in the vehicle control. However, RP3 treatment completely inhibited the increase in extracellular AR after reperfusion. RP3 treatment exerted no effect on the changes in extracellular ascorbate or tissue PO2 throughout the experimental period. In conclusion, neutrophils are a major source of oxygen radicals during reperfusion after focal cerebral ischemia.

Animals↗

PubMed2004

Red wine administration to apolipoprotein E-deficient mice reduces their macrophage-derived extracellular matrix atherogenic properties.

Proteoglycans (PGs) from the arterial extracellular matrix (ECM) contribute to the trapping of LDL and oxidized LDL (Ox-LDL) in the arterial wall, a phenomenon called "lipoprotein retention". Moreover, we have shown that subsequent to their binding to the matrix, LDL and Ox-LDL are taken up by macrophages. Oxidative stress significantly increases macrophage secretion of ECM-PGs, lipoprotein binding to the ECM and the uptake of ECM-retained lipoproteins by macrophages. The aim of the present study was to determine whether red wine administration to atherosclerotic mice would affect their peritoneal macrophage-derived extracellular matrix properties, such as the glycosaminoglycan content and the ability to bind LDL. In addition, we questioned the ability of LDL bound to the mice peritoneal macrophages-derived ECM to be taken up by macrophages. Red wine administration to atherosclerotic mice did not affect the mice peritoneal macrophages-derived ECM glycosaminoglycan content but it significantly reduced the mice peritoneal macrophages-derived ECM ability to bind LDL and the subsequent uptake of ECM-retained LDL by the macrophages. The present study thus clearly demonstrated the inhibitory effect of red wine consumption by E0 mice on their peritoneal macrophage-derived extracellular matrix atherogenic properties.

Animals↗

PubMed1995

Relationship of amyloid beta/A4 protein to the neurofibrillary tangles in Guamanian parkinsonism-dementia.

The Chamorro population of the island of Guam is highly susceptible to a disease called lytico-bodig (LB), which clinically resembles a mixture of amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer disease (AD). The disease is characterized by the widespread development of neurofibrillary tangles in the central nervous system. These tangles have an immunohistochemical profile indistinguishable from that seen in AD. We studied by immunohistochemistry the occurrence of intracellular and extracellular neurofibrillary tangles in LB in the entorhinal cortex, hippocampus and substantia nigra using antibodies to tau protein and ubiquitin. We also studied the relationship of these tangles to amyloid precursor protein (APP) and its beta-amyloid fragment (BAP), using multiple antibodies to BAP and other APP sequences. In advanced cases of LB, the development of neurofibrillary tangles was far more severe than in advanced cases of AD. Virtually all neurons of CA-1 and the subiculum were lost and only ghost tangles remained. In areas dominated by such extracellular tangles, BAP deposits were frequently observed developing around the fibers of ghost tangles. In some cases, the deposits covered only a few of the fibers, but in others, they seemed to envelope the complete tangle. The deposits were thioflavin S and Congo red positive, indicating that the BAP was in a consolidated form. We describe these entities as "tangle-associated amyloid deposits". Such BAP deposits have previously been described in some cases of AD, dementia pugilistica and LB. However, we found them in all cases of LB with dementia in the hippocampal-entorhinal areas and in most cases in the substantia nigra. They do not evolve from diffuse BAP deposits since they are remote from them, and they do not trap dystrophic neurites. The fact that extracellular tangle material can act as a nidus for BAP build-up in LB suggests that further consideration needs to be given to the ways in which extracellular BAP deposits are formed.

Adult↗

PubMed2000

Tumor necrosis factor receptor-associated periodic syndrome: a novel syndrome with cutaneous manifestations.

BACKGROUND: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an inflammatory disorder characterized by prolonged episodes of periodic fever and localized inflammation and dominantly inherited mutations in TNFRSF1A, the gene encoding the 55-kDa tumor necrosis factor receptor. To our knowledge, the cutaneous pathologic characteristics of TRAPS have not been described previously. OBJECTIVES: To characterize the dermatologic manifestations of TRAPS by clinical, microscopic, and molecular methods, and to investigate its immunophenotype. DESIGN, SETTING, AND PATIENTS: At the National Institutes of Health Clinical Center, Bethesda, Md, a tertiary care referral center, 25 patients with a clinical and molecular diagnosis of TRAPS were evaluated clinically and 10 biopsy specimens of lesional skin were examined by light microscopy and immunohistochemistry. Patients were screened for mutations in TNFRSF1A, the gene coding for the p55 tumor necrosis factor receptor. MAIN OUTCOME MEASURES: Clinical, light microscopic, and immunohistochemical features. RESULTS: The skin eruption usually lasted 4 to 21 days (mean, 13 days). Of 25 patients, 21 (84%) presented with migratory erythematous macules and patches and 10 (40%) had edematous dermal plaques. Conjunctivitis, characterized by pain and redness and/or periorbital edema, was present in 11 patients (44%). Most patients had their first skin eruption during the first 2 years of life. All patients had fever associated with the skin eruption. Most patients had associated abdominal pain (22 [88%]) and myalgia (20 [80%]). Other symptoms included arthralgia (13 [52%]), pleuritic chest pain (10 [40%]), and headache (17 [68%]). Microscopic examination of 10 biopsy specimens of lesional skin showed a superficial and deep perivascular and interstitial infiltrate of lymphocytes and monocytes. None of the biopsy specimens showed multinucleated macrophages or granulomatous or leukocytoclastic vasculitis. The results of immunohistochemistry showed a perivascular infiltrate of CD3+, CD4+, CD8+, CD68+, CD79a-, and CD20- cells. All the mutations were missense mutations in exons 2 through 4 of TNFRSF1A, directly affecting the extracellular domain of the protein. CONCLUSIONS: TRAPS is characterized by a spectrum of dermatologic findings, including migratory patches, edematous plaques, periorbital edema, and/or conjunctivitis. TRAPS is characterized by a perivascular dermal infiltrate of lymphocytes and monocytes.

Adolescent↗

PubMed1996

Sequence analysis and regulation of a gene encoding a cuticle-degrading serine protease from the nematophagous fungus Arthrobotrys oligospora.

The nematode trapping fungus Arthrobotrys oligospora produces an extracellular serine protease (designated PII) that immobilizes free-living nematodes in bioassays and hydrolyses proteins of the nematode cuticle. Peptides were isolated from PII and partly sequenced. Three internal peptide sequences were used to design synthetic oligonucleotides, which allowed the subsequent isolation of the gene encoding PII from a genomic library. The deduced amino acid sequence indicated that PII is synthesized as a preproenzyme containing the mature enzyme, a signal sequence and a propeptide that are removed before the enzyme is secreted into the medium. The primary sequence of PII displayed a high degree of similarity with several other serine proteases of ascomycetes belonging to the subtilisin family. Northern analysis demonstrated that PII was expressed when the fungus was starved of nitrogen and carbon and that the expression was significantly stimulated by the addition to the medium of various soluble and insoluble proteins, including fragments of nematode cuticle. The levels of the mRNA as well as the proteolytic activity of PII were repressed in the presence of more easily metabolized forms of nitrogen (including ammonia, nitrate and amino acids) or glucose. The activity of the enzyme was almost completely inhibited by the peptide Phe-Val, as well as by the amino acid Phe, without a corresponding decrease in mRNA level. Notably, peptides with similar structures are known to be secreted by the host (nematode) and to stimulate the production of infection structures (traps) of the fungus.

Amino Acid Sequence↗

PubMed2005

Detection and characterization of the product of hydroethidine and intracellular superoxide by HPLC and limitations of fluorescence.

Here we report the structural characterization of the product formed from the reaction between hydroethidine (HE) and superoxide (O(2)(.-)). By using mass spectral and NMR techniques, the chemical structure of this product was determined as 2-hydroxyethidium (2-OH-E(+)). By using an authentic standard, we developed an HPLC approach to detect and quantitate the reaction product of HE and O(2)(.-) formed in bovine aortic endothelial cells after treatment with menadione or antimycin A to induce intracellular reactive oxygen species. Concomitantly, we used a spin trap, 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO), to detect and identify the structure of reactive oxygen species formed. BMPO trapped the O(2)(.-) that formed extracellularly and was detected as the BMPO-OH adduct during use of the EPR technique. BMPO, being cell-permeable, inhibited the intracellular formation of 2-OH-E(+). However, the intracellular BMPO spin adduct was not detected. The definitive characterization of the reaction product of O(2)(.-) with HE described here forms the basis of an unambiguous assay for intracellular detection and quantitation of O(2)(.-). Analysis of the fluorescence characteristics of ethidium (E(+)) and 2-OH-E(+) strongly suggests that the currently available fluorescence methodology is not suitable for quantitating intracellular O(2)(.-). We conclude that the HPLC/fluorescence assay using HE as a probe is more suitable [corrected] for detecting intracellular O(2)(.-).

Animals↗

PubMed1996

Role of platelet-activating factor and thromboxane A2 in radical production during ischemia and reperfusion of the rat brain.

Oxygen radicals produced by activated neutrophils have been involved in brain injury during ischemia-reperfusion. Platelet-activating factor (PAF) is a candidate as one of the mediators of neutrophil activation during cerebral ischemia-reperfusion. Recent evidence indicates that PAF-induced neutrophil activation is mediated by thromboxane A2 (TXA2). To study the role of PAF and TXA2 in radical production during cerebral ischemia-reperfusion, we evaluated the effects of a PAF antagonist, Y-24180, and a TXA2 antagonist, S-1452, on radical formation in rats with 1 h middle cerebral artery (MCA) occlusion. In the present study, we employed a new electron spin resonance (ESR) method coupled with brain microdialysis. The method uses the endogenous ascorbyl radical (AR) concentration as a marker of oxygen radicals and requires no spin-trapping agents. In the vehicle controls, extracellular AR from the ischemic brain cortex decreased during MCA occlusion. Following reperfusion, AR significantly increased at 30 mm and 1 h, returned to near the basal levels at 2 h, and increased again at 24 h after reperfusion. In the rats treated with S-1452 or Y-24180, AR decreased during MCA occlusion to the same extent as in the vehicle control. However, pretreatment with Y-24180 or S-1452 significantly attenuated the increase in extracellular AR after reperfusion, while it exerted no effect on the changes in extracellular ascorbate or tissue pO2 throughout the experimental period. In conclusion, PAF and TXA2 might contribute to cerebral ischemia-reperfusion injury by increasing the generation of oxygen radicals.

Animals↗

PubMed1999

Accumulation of co-localised unesterified cholesterol and neutral lipids within vacuolised elastin fibres in athero-prone areas of the human aorta.

To investigate whether there are alterations of elastin fibres in the arterial intima at the pre-atherosclerotic stage, grossly normal areas of human thoracic aorta were taken soon after death from 13 healthy trauma victims whose ages ranged from 16 to 40 years. Two areas were compared: atherosclerosis-prone (AP) areas localised to the dorsal aspect of the aorta along the rows of intercostal branch origins, and atherosclerosis-resistant (AR) areas from the ventral aorta. Electron microscopic analysis combined with cytochemical staining was applied. Unesterified cholesterol was identified using the filipin-staining technique while neutral lipids were visualised by the OTO-technique. Intimal features were studied by combining the filipin-staining and the OTO-technique. Electron microscopical examination showed that in both AR and AP areas, some elastin fibres in the intima were vacuolised. Unesterified cholesterol was found to be predominantly localised in the musculoelastic layer, in particular, inside the vacuolised elastin fibres. This localisation was seen in all 13 AP areas studied in contrast to the AR areas where it was observed in only four of 13 aortas studied (P < 0.0005, chi2-test). Accumulation of neutral lipids inside vacuolised elastin fibres was found in five out of 13 AP areas but was not observed in any of the AR areas (P=0.01, chi2). A combination of the filipin-staining and OTO-techniques showed that some deposits of neutral lipids and unesterified cholesterol within vacuolised elastin fibres were independently located from each other, but more frequently, neutral lipids were co-located with unesterified cholesterol. The present observations indicate a difference between AP and AR intimal areas which, in particular, relates to the structure of elastin fibres in the musculoelastic layer. The observations suggest that alterations of the extracellular matrix are involved in the trapping and retention of cholesterol and neutral lipids within the intima at an early stage in the development of atherosclerotic lesions.

Adolescent↗

PubMed1984

Nonenzymatic glycosylation and the pathogenesis of diabetic complications.

Glucose chemically attaches to proteins and nucleic acids without the aid of enzymes. Initially, chemically reversible Schiff base and Amadori product adducts form in proportion to glucose concentration. Equilibrium is reached after several weeks, however, and further accumulation of these early nonenzymatic glycosylation products does not continue beyond that time. Subsequent reactions of the Amadori product slowly give rise to nonequilibrium advanced glycosylation end-products which continue to accumulate indefinitely on longer-lived molecules. Excessive formation of both types of nonenzymatic glycosylation product appears to be the common biochemical link between chronic hyperglycemia and a number of pathophysiologic processes potentially involved in the development of long-term diabetic complications. The major biological effects of excessive nonenzymatic glycosylation include: inactivation of enzymes; inhibition of regulatory molecule binding; crosslinking of glycosylated proteins and trapping of soluble proteins by glycosylated extracellular matrix (both may progress in the absence of glucose); decreased susceptibility to proteolysis; abnormalities of nucleic acid function; altered macromolecular recognition and endocytosis; and increased immunogenicity.

Blood Glucose↗

PubMedDate not supplied

In vitro study of low density lipoprotein--collagen interaction.

Possibility of LDL--collagen complex formation was investigated in vitro by biochemical assay and electron microscopy. Types I and III collagen isolated from bovine thoracic aorta were incubated with human low density lipoproteins (LDL) at physiological ionic strength, pH and temperature. Biochemical quantification showed that 10-20 micrograms LDL (cholesterol) were bound per 100 micrograms collagen, binding of type III being slightly more pronounced (17%) than that of type I (11%). Binding was in inversely proportional to the extent of fibrillation. The increase of ionic strength and pH reduced the binding, indicating the electrostatic nature of the interaction. These observations suggest a possible trapping mechanism of LDL in the extracellular matrix by means of collagen, which may be relevant for the development of the atherosclerotic lesions.

Arteriosclerosis↗

PubMed2006

Probing receptor binding activity of interleukin-8 dimer using a disulfide trap.

Interleukin-8 (IL-8), a member of the chemokine superfamily, exists as both monomers and dimers, and mediates its function by binding to neutrophil CXCR1 and CXCR2 receptors that belong to the G protein-coupled receptor class. It is now well established that the monomer functions as a high-affinity ligand, but the binding affinity of the dimer remains controversial. The approximately 1000-fold difference between monomer-dimer equilibrium constant (microM) and receptor binding constant (nM) of IL-8 does not allow receptor-binding affinity measurements of the native IL-8 dimer. In this study, we overcame this roadblock by creating a "trapped" nondissociating dimer that contains a disulfide bond across the dimer interface at the 2-fold symmetry point. The NMR studies show that the structure of this trapped dimer is indistinguishable from the native dimer. The trapped dimer, compared to a trapped monomer, bound CXCR1 with approximately 70-fold and CXCR2 with approximately 20-fold lower affinities. Receptor binding involves two interactions, between the IL-8 N-loop and receptor N-domain residues, and between IL-8 N-terminal and receptor extracellular loop residues. In contrast to a trapped monomer that bound an isolated CXCR1 N-domain peptide with microM affinity, the trapped dimer failed to show any binding, indicating that dimerization predominantly perturbs the binding of only the N-loop residues. These results demonstrate that only the monomer is a high-affinity ligand for both receptors, and also provide a structural basis for the lower binding affinity of the dimer.

Amino Acid Substitution↗

PubMed2004

[18F]-2-fluoro-2-deoxyglucose transport kinetics as a function of extracellular glucose concentration in malignant glioma, fibroblast and macrophage cells in vitro.

FDG-PET is used to measure the metabolic rate of glucose. Transport and phosphorylation determine the amount of hexose analog that is phosphorylated and trapped. Competition occurs for both events, such that extracellular glucose concentration affects the FDG image. This study investigated the effect of glucose concentration on the rate of FDG accumulation in three cell lines. The results show that extracellular glucose concentration has a greater impact on the rate of FDG accumulation than the relative abundance of GLUT transporter subtypes.

Animals↗

PubMed1987

Extracellular killing of Trypanosoma cruzi amastigotes by human eosinophils.

Granules released from human eosinophils upon interaction with Trypanosoma cruzi amastigotes in vitro were seen attached to the surface of non-internalized parasites by electron microscopy. Amastigote damage was preceded by the binding of eosinophil granule material to its membrane, and eosinophil granule major basic protein (MBP) bound to the parasite surface was readily detectable. Additional evidence of eosinophil cytotoxicity for extracellular amastigotes was the observation that amastigotes trapped between two eosinophils, without being ingested by either one, were destroyed at the interface. Amastigotes isolated from the spleens of infected mice or grown in culture were similarly sensitive to the lytic effects of purified MBP. These results demonstrate the ability of human eosinophils to lyse T. cruzi amastigotes extracellularly in the absence of antibody and suggest that MBP may be involved in the effect. Thus, eosinophils, known to be capable of destroying phagocytosed amastigotes, could also contribute to the clearance of these parasites through extracellular killing.

Animals↗