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PubMed2002

Effect of sulphur inoculated with Thiobacillus on soil salinity and growth of tropical tree legumes.

A greenhouse experiment was carried out with the objective of evaluating the effects of the elementary sulphur inoculated with Thiobacillus, compared with gypsum, in the amendment of a alluvial sodic saline soil from the Brazilian semiarid region, irrigated with saline water and grown with the tropical legumes leucena and mimosa. The treatments consisted of levels of sulphur (0; 300 and 600 kg/ha) and gypsum (1,200 and 2,400 kg/ha), irrigation using different waters containing the salts NaHCO3, MgCl2, CaCl2, NaCl and KCl, with different electrical conductivities (ECs: 0.2. 6.1 and 8.2 dS/m at 25 degrees C). Based on the results it appears that saline water increased exchangeable Na+, K+, Ca2+, Mg2+, and soil pH. Sulphur inoculated with Thiobacillus was more efficient than gypsum in the reduction of the exchangeable sodium of the soil and promoting leaching of salts, especially sodium. Sulphur inoculated with Thiobacillus reduced the EC of the soil saturation extract to levels below that adopted in soil classification of sodic or saline sodic. Leucena was more tolerant to salinity and mimosa more resistant to acidity promoted by sulphur inoculated with Thiobacillus.

Brazil↗
PubMed2005

Perturbed reproductive development in salt-treated Sorghum bicolor: a consequence of modifications in regulation networks?

In Sorghum bicolor, tolerance to salinity is improved by a 3-week treatment with 150 mM NaCl during early vegetative development. However, a strong decrease in fertility is also observed, suggesting that reproductive development becomes perturbed by this adaptive response to salinity. This study is an attempt to clarify the origin of such a paradoxical phenomenon. The relationships between end-cycle characters are modified by the NaCl treatment: some linkages disappear, while others are strengthened, especially those linking fertility with plant height. In parallel, a transient reduced level of linkage between leaf characters is observed around the unfolding of the eighth to the tenth leaves, defining a critical period in vegetative development separating two discrete phases. A relationship is observed between events occurring during this short critical period and the NaCl-induced perturbations in fertility. This suggests that reproductive development is conditioned by the influence of salinity on events occurring during a short period of vegetative development, independently of the level of tolerance to salinity quantified by the rate of vegetative growth.

Adaptation, Physiological↗
PubMed2002

Salt-tolerant mutants in glycophytic salinity response (GSR) genes in Catharanthus roseus.

The periwinkle Catharanthus roseus shares glycophytic properties of crop plants. To contribute towards an understanding of the glycophytic response to salinity, large populations of M(2) seeds having an origin in nitroso-methyl urea and ethyl methane sulphonate treatments were screened for germination with 250 mM of NaCl. Out of the nine mutant lines so recovered, which tolerated salt stress due to loss of the normal glycophytic salinity response ( GSR), the characteristics of six gsr mutants are reported here. All six, gsr-1 to gsr-6, differed from the wild-type in both seedling and adult-plant morphological characters beside being salt tolerant. The mutations in them were inherited as monogenic recessive alleles at the corresponding wild-type loci. The trans-complementation tests revealed that the gsr-1 to gsr-6 mutants specified six complementation groups. The mutant seedlings generally accumulated more proline and glycine betaine, constitutively, than the wild-type. The mutant plants transpired lower amounts of water and accumulated higher amounts of proline under drought stress. It was inferred that the products of the six GSR genes defined here are involved in the regulation of salt stress, as well as cell division, developmental and/or morphogenetic pathway(s), in C. roseus.

Adaptation, Physiological↗
PubMed2006

Halocafeteria seosinensis gen. et sp. nov. (Bicosoecida), a halophilic bacterivorous nanoflagellate isolated from a solar saltern.

Recently, heterotrophic nanoflagellates (HNF) have been reported to actively ingest prokaryotes in high salinity waters. We report the isolation and culture of an HNF from a Korean saltern pond of 300 per thousand salinity. The organism is biflagellated with an acronematic anterior flagellum and never glides on surfaces. The mitochondria have tubular cristae. Neither transitional helix nor spiral fiber were observed in the transition zones of the flagella. The cell has a cytostome supported by an arc of eight microtubules, suggesting that our isolate is a bicosoecid. Our isolate had neither mastigonemes, lorica, body scales, nor cytopharynx and thus could not be placed in any of the presently described bicosoecid genera. Phylogenetic analysis of 18S rRNA gene sequences from stramenopiles confirmed the bicosoecid affinities of our isolate, but did not place it within any established genus or family. Its closest relatives include Caecitellus and Cafeteria. The optimal range of growth temperature was 30-35 degrees C. The isolated HNF grew optimally at 150 per thousand salinity and tolerated up to 363 per thousand salinity, but it failed to grow below 75 per thousand salinity, indicating that it could be a borderline extreme halophile. On the basis of its morphological features and position in 18S rRNA trees we propose a novel genus for our isolate; Halocafeteria, n. gen. The species name Halocafeteria seosinensis sp. nov. is proposed.

Animals↗
PubMed2004

Phytoremediation of petroleum hydrocarbons in tropical coastal soils. I. Selection of promising woody plants.

GOAL, SCOPE AND BACKGROUND: This glasshouse study is aimed at evaluating tropical plants for phytoremediation of petroleum hydrocarbon-contaminated saline sandy subsurface soils. Tropical plants were selected for their ability to tolerate high salinity and remove No. 2 diesel fuel in coastal topsoil prior to further investigation of the phytoremediation feasibility in deep contaminated soils. The residual petroleum-hydrocarbon contaminant at the John Rogers Tank Farm site, a former petroleum storage facility, at Hickam Air Force Base, Honolulu, Hawaii, is located in a coastal area. It lies below a layer of silt in the subsurface, in loamy sand characterized by moderate salinity and high pH. Little is known regarding the ability of tropical plants to remediate petroleum hydrocarbon-contaminated subsurface soil in Hawaiian and other Pacific Island ecosystems although suitable plants have been identified and utilized for bioremediation in surface soil or marine sediments. METHODS: The experiments were conducted in long narrow pots under glasshouse conditions in two phases. A preliminary experiment was done with nine tropical plants: kiawe (Prosopis pallida), milo (Thespesia populnea), common ironwood (Casuarina equisetifolia), kou (Cordia subcordata), tropical coral tree (Erythrina variegata), false sandalwood (Myoporum sandwicense), beach naupaka (Scaevola sericea), oleander (Nerium oleander), and buffelgrass (Cenchrus ciliaris). These plants were screened for resistance to high salinity treatment (2% NaCl) and two diesel fuel levels (5 and 10 g No. 2 diesel fuel/kg soil) in separate treatments. Plants that showed good tolerance of both factors were further evaluated in a second phase for their efficacy in the phytoremediation of diesel-fuel petroleum hydrocarbons under moderate salinity treatment (1% NaCl). RESULTS: Tropical coral tree and buffelgrass were susceptible to either 2% NaCl or diesel fuel at 10 g/kg soil, but tolerant of diesel fuel at 5 g/kg soil. Kiawe, milo, kou, common ironwood, N. oleander, beach naupaka and false sandalwood were tolerant of high salinity (2% NaCl) or high diesel fuel level (10 g/kg soil). These seven plants were also tolerant of the combined adverse effects of a moderate salinity (1% NaCl) and 10 g diesel fuel/kg soil. Three trees, kiawe, milo and kou significantly accelerated the degradation of petroleum hydrocarbons in the soil spiked with 10 g diesel fuel/kg soil under a moderate salinity treatment (1% NaCl). CONCLUSION: Thus the tropical woody plants, kiawe, milo and kou showed potential for use in phytoremediation of petroleum hydrocarbons in coastal tropical soils. RECOMMENDATIONS AND OUTLOOK: Two fast growing trees, milo and kou, appeared promising for further phytoremediation evaluation in experiments that simulate the soil profile at the field site.

Biodegradation, Environmental↗
PubMed1993

Differential responses of nitrogen-fixing cyanobacteria to salinity and osmotic stresses.

Two nitrogen-fixing Anabaena strains were found to be differentially tolerant to salinity and osmotic stresses. Anabaena torulosa, a brackish-water, salt-tolerant strain, was relatively osmosensitive. Anabaena sp. strain L-31, a freshwater, salt-sensitive strain, on the other hand, displayed significant osmotolerance. Salinity and osmotic stresses affected nitrogenase activity differently. Nitrogen fixation in both of the strains was severely inhibited by the ionic, but not by the osmotic, component of salinity stress. Such differential sensitivity of diazotrophy to salinity-osmotic stresses was observed irrespective of the inherent tolerance of the two strains to salt-osmotic stress. Exogenously added ammonium conferred significant protection against salinity stress but was ineffective against osmotic stress. Salinity and osmotic stresses also affected stress-induced gene expression differently. Synthesis of several proteins was repressed by salinity stress but not by equivalent or higher osmotic stress. Salinity and osmotic stresses induced many common proteins. In addition, unique salt stress- or osmotic stress-specific proteins were also induced in both strains, indicating differential regulation of protein synthesis by the two stresses. These data show that cyanobacterial sensitivity and responses to salinity and osmotic stresses are distinct, independent phenomena.

Journal Article↗
PubMed2003

Plant responses to drought, salinity and extreme temperatures: towards genetic engineering for stress tolerance.

Abiotic stresses, such as drought, salinity, extreme temperatures, chemical toxicity and oxidative stress are serious threats to agriculture and the natural status of the environment. Increased salinization of arable land is expected to have devastating global effects, resulting in 30% land loss within the next 25 years, and up to 50% by the year 2050. Therefore, breeding for drought and salinity stress tolerance in crop plants (for food supply) and in forest trees (a central component of the global ecosystem) should be given high research priority in plant biotechnology programs. Molecular control mechanisms for abiotic stress tolerance are based on the activation and regulation of specific stress-related genes. These genes are involved in the whole sequence of stress responses, such as signaling, transcriptional control, protection of membranes and proteins, and free-radical and toxic-compound scavenging. Recently, research into the molecular mechanisms of stress responses has started to bear fruit and, in parallel, genetic modification of stress tolerance has also shown promising results that may ultimately apply to agriculturally and ecologically important plants. The present review summarizes the recent advances in elucidating stress-response mechanisms and their biotechnological applications. Emphasis is placed on transgenic plants that have been engineered based on different stress-response mechanisms. The review examines the following aspects: regulatory controls, metabolite engineering, ion transport, antioxidants and detoxification, late embryogenesis abundant (LEA) and heat-shock proteins.

Disasters↗
PubMed1986

A double-blind randomized comparison of the effect and tolerance of Varidase versus saline when instilled in the urinary bladder in patients with catheter problems.

Thirty-eight patients with problems with their urinary catheters were randomly treated with Varidase or normal saline solution once a day for 10 days. Photographs were taken by using a cystoscope before treatment, at day 10 and day 24 after the commencement of treatment. The photographs were evaluated according to the occurrence of pus, debris, coagula and rubor. In the Varidase group the improvements from baseline to day 10 and day 24 were statistically significant (p less than 0.05) in all parameters while there were no statistically significant improvements in the saline group. Comparing the two treatment groups, regarding the changes from baseline to day 10 and day 24, it was statistically demonstrated that Varidase was significantly more effective than saline in all parameters (p less than 0.05). In conclusion, this study shows that Varidase effectively cleans the urinary bladder from pus, fibrin, necrotic tissue and blood clots.

Aged↗
PubMedDate not supplied

Red cell tolerance of admixture with heated saline.

Red cell stability in the face of thermal stress has been evaluated only in the setting of prolonged incubation. This study was conducted to determine red cell tolerance of rapid mixture with heated saline, which exposes red cells to heat only until thermal equilibration, which is a matter of seconds. Half-units of 35-day-old red cells stored in CPDA-1 were mixed at 6 to 10 degrees C in the blood container with an equal weight of 60, 70, or 80 degrees C saline. This resulted in mean mixture temperatures of 30.9, 37.5, and 42.6 degrees C, respectively. Controls consisted of the same mixture, but with 6 to 10 degrees C saline. The red cells in the mixtures were assessed for osmotic fragility, and the supernatant was examined for plasma hemoglobin and potassium. Neither osmotic fragility curves nor supernatant hemoglobin or potassium changed significantly with saline temperatures of 60 or 70 degrees C. When 80 degrees C saline was used, osmotic fragility, supernatant hemoglobin, and potassium all increased significantly (p less than 0.01) over control values. Red cells tolerate rapid mixture with 70 degrees C saline without hemolysis or change in osmotic fragility.

Erythrocyte Transfusion↗
PubMed2002

The effects of salinity and sodicity upon nodulation and nitrogen fixation in chickpea (Cicer arietinum).

Production of grain legumes is severely reduced in salt-affected soils because their ability to form and maintain nitrogen-fixing nodules is impaired by both salinity and sodicity (alkalinity). Genotypes of chickpea, Cicer arietinum, with high nodulation capacity under stress were identified by field screening in a sodic soil in India and subsequently evaluated quantitatively for nitrogen fixation in a glasshouse study in a saline but neutral soil in the UK. In the field, pH 8.9 was the critical upper limit for most genotypes studied but genotypes with high nodulation outperformed all others at pH 9.0-9.2. The threshold limit of soil salinity for shoot growth was at ECe 3 dS m(-1), except for the high-nodulation selection for which it was ECe 6. Nodulation was reduced in all genotypes at salinities above 3 dS m(-1) but to a lesser extent in the high-nodulation selection, which proved inherently superior under both non-saline and stress conditions. Nitrogen fixation was also much more tolerant of salinity in this selection than in the other genotypes studied. The results show that chickpea genotypes tolerant of salt-affected soil have better nodulation and support higher rates of symbiotic nitrogen fixation than sensitive genotypes.

Algorithms↗
PubMed2006

Variable tolerance of wetland tree species to combined salinity and waterlogging is related to regulation of ion uptake and production of organic solutes.

Melaleuca cuticularis and Casuarina obesa occur in wetlands, whereas Banksia attenuata occurs in adjacent well-drained sandy soils. Salt and waterlogging tolerances in these tree species were studied, as the levels of these stresses have increased in south-western Australia. Seedlings were exposed to 0.01, 200 or 400 mm NaCl, with or without waterlogging, in a sand culture with nutrient solution for 22 d in a glasshouse. Melaleuca cuticularis and C. obesa survived all treatments, and generally maintained high rates of net photosynthesis. Banksia attenuata tolerated neither waterlogging nor salinity. Salt tolerance of M. cuticularis and C. obesa was associated with the regulation of foliar sodium (Na+), chloride (Cl-) and potassium (K+) concentrations. Under saline-waterlogged conditions, this regulation was maintained in M. cuticularis, but was reduced in C. obesa. Foliage of these two species also contained appreciable levels of compatible organic solutes: methyl proline in M. cuticularis and proline in C. obesa; in both cases the concentrations increased at higher salinity. Melaleuca cuticularis formed a higher proportion of aerenchyma in adventitious roots than C. obesa, so enhanced internal root aeration in M. cuticularis might contribute to its higher tolerance of combined salinity and waterlogging.

Acclimatization↗
PubMed2001

Salt tolerance in aquatic macrophytes: possible involvement of the antioxidative enzymes.

Possible involvement of the antioxidative enzymes in salt tolerance was investigated in three submerged aquatic macrophytes, viz. Hydrilla verticillata, Najas indica and Najas gramenia, which differed in their tolerance to salinity. NaCl in light resulted in significant decrease in the chlorophyll a/b ratio in H. verticillata, which was significantly neutralized by the presence of DABCO (diazabicyclo[2.2.2]octane), sodium benzoate or mannitol along with the NaCl in the exposure medium indicating induction of oxidative stress upon salt treatment. All the three test species showed enhanced activity of superoxide dismutase (SOD; EC 1.15.1.1) and peroxidases (EC 1.11.1.7) upon exposure to either NaCl or SWS (seawater salinity); the increases in their activity in response to NaCl were positively correlated with the salt tolerance of the plants. Only N. gramenia showed considerable increase in the activity of catalase (EC 1.11.1.6), while only H. verticillata exhibited significant increase in the activity of ascorbate peroxidase (EC 1.11.1.11) in response to the salt treatment. A higher constitutive level of the antioxidative enzymes in the salt-tolerant N. gramenia than in the salt-sensitive H. verticillata coupled with significant increase in the activity of these enzymes, particularly of catalase and SOD, in the former upon salinity treatment suggested their active involvement in salt tolerance. The oxidative stress induced upon the salt treatment also indicated a possible involvement of the antioxidative enzymes in the process. The ion interaction study revealed significant modifying effect of Ca(2+), and also of Mg(2+) and K(+), on the changes induced by Na(+) in the activity of catalase and SOD suggesting that relative build-up of these ions inside cells could be of much importance in regulation of synthesis of antioxidative enzymes.

Journal Article↗
PubMed2003

Effect of some abiotic factors on the biological activity of Gluconacetobacter diazotrophicus.

AIMS: The effect of some abiotic factors, dryness, heat and salinity on the growth and biological activity of Gluconacetobacter diazotrophicus, and the influence of a salt stress on some enzymes involved in carbon metabolism of these bacteria is studied under laboratory conditions. METHODS AND RESULTS: Strain PAL-5 of G. diazotrophicus was incubated under different conditions of drying, heat and salinity. Cells showed tolerance to heat treatments and salt concentrations, and sensitivity to drying conditions. Higher NaCl dosage of 150 and 200 mmol l -1 limited its growth and drastically affected the nitrogenase activity and the enzymes glucose dehydrogenase, alcohol dehydrogenase, fumarase, isocitrate dehydrogenase and malate dehydrogenase. CONCLUSIONS: Gluconacetobacter diazotrophicus, despite its endophytic nature, tolerated heat treatments and salinity stress, but its nitrogenase activity and carbon metabolism enzymes were affected by high NaCl dosage. SIGNIFICANCE AND IMPACT OF THE STUDY: The investigation of the biological activity of G. diazotrophicus in response to different abiotic factors led to more knowledge of this endophyte and may help to clarify pathways involved in its transmission into the host plant.

Acetobacter↗
PubMed1985

T cell tolerance studied at the level of antigenic determinants. I. Latent reactivity to lysozyme peptides that lack suppressogenic epitopes can be revealed in lysozyme-tolerant mice.

Whether T cell tolerance represents direct inactivation of antigen-specific T cells via recognition of antigen plus major histocompatibility complex, or via T suppressor (Ts) cells, or a combination of these mechanisms, remains to be clarified. This problem was investigated using a novel approach based on the finding in several systems that T helper/proliferative (Th/Tp) cell-inducing antigenic determinants are dissociable from Ts cell-inducing determinants. Thus, peptide probes containing known sites that stimulate T proliferative activity, as well as peptides from distinct sites assumed to bear Ts-inducing determinants, were used in studying hen (chicken) eggwhite lysozyme (HEL)-tolerant mice. The clear prediction from clonal deletion model is that Th/Tp response potential to short peptides in the tolerant mouse would not exist, while regulatory suppression models predict the coexistence of antigen-reactive cells and antigen-specific regulatory cells that prevent their expression. Adult mice, treated with 2 mg HEL in saline, were tolerant to HEL in complete Freund's adjuvant (CFA). Latent T cell proliferative responses could be revealed to determinants within two HEL peptide probes, which lacked the amino-terminal region of the molecule. This responsiveness suggested two conclusions: first, Ts cells directed against the amino terminus of lysozyme exist in the tolerant genetic responder B10.A; second, these Ts regulate the activity of functional antigen-reactive T cells directed against epitopes elsewhere on the molecule, but only in the presence of the complete molecule, HEL. Examination of neonatally induced tolerance did not reveal any latent responsiveness, supporting the hypothesis that clonal deletion or anergy is the relevant mechanism in this situation. Possible reservations in these explanations of the two tolerant states, plus analysis of the more complex "split tolerance" resulting from 20 mg HEL in saline treatment in adults, are discussed. The approach of dissociation of proliferation-inducing determinants from suppression-inducing determinants clarifies our understanding of the tolerant state and holds promise for more definitive exploration of mechanisms of T cell tolerance.

Aging↗
PubMed2004

Stabilization of model membranes during drying by compatible solutes involved in the stress tolerance of plants and microorganisms.

Many organisms accumulate compatible solutes under environmental stress conditions. Cyanobacteria accumulate compatible solutes in response to increased external salinity, with tolerance increasing from Suc (sucrose) or trehalose to 2-O-(alpha-D-glucopyranosyl)-glycerol and glycinebetaine accumulating species. It is not clear how these different solutes influence salt tolerance. One possible explanation may be a differential ability of these solutes to stabilize membranes under stress conditions. We therefore performed drying experiments with liposomes in the presence of compatible solutes. Suc, trehalose and sorbitol protected liposomes from leakage of a soluble marker and from membrane fusion during drying and rehydration. 2-O-(alpha-D-glucopyranosyl)-glycerol was less effective and glycinebetaine showed hardly any effect. In combination with Suc, the latter two solutes showed improved protection. Lipid-phase transitions are known to contribute to solute leakage from liposomes. We determined phase transitions in dry membranes in the absence or presence of the solutes, using Fourier-transform infrared spectroscopy. The ability of the solutes to decrease the phase transition temperature corresponded closely to their ability to protect the liposomes against solute leakage. All solutes interacted with the phosphate in the lipid headgroups. The magnitude of the shift in the asymmetric P=O stretching vibration correlated closely with the lipid-phase transition temperature. This indicates that the degree of membrane protection afforded by the solutes is mainly determined by their ability to interact with the membrane lipids. However, this is not a determinant of cellular protection against salt stress, as the solutes show a reverse order when ranked with regard to protection against these stresses.

Betaine↗
PubMed2003

Long-term hyposaline and hypersaline stresses produce distinct antioxidant responses in the marine alga Dunaliella tertiolecta.

Tolerance to salinity stress in higher plants correlates to levels of antioxidant enzymes and/or substrates. Do hyperosmotic and hypoosmotic stress induce antioxidant responses in salt tolerant algae, and if so, are these responses the same for both excess and minimal salinity? To answer these questions, cultures of the marine alga Dunaliella tertiolecta (Chlorophyta) were grown in seven salinities covering a 60-fold range from 0.05 to 3.0 mol/L NaCl. Long-term effects of salinity on growth and antioxidant parameters were determined. Growth rates were reduced at the salinity extremes (0.05 mol/L NaCl and 3 mol/L NaCl) indicating the cultures were stressed. The levels of six antioxidant enzymes and three antioxidant substrates were quantified at these growth salinities. Compared to growth at optimum salinities (i.e. 0.2-0.5 mol/L NaCl), high salinities produced a 260% increase in monodehydroascorbate reductase, a doubling of ascorbate peroxidase activity and a three-fold increase in the rate of dark respiration. Cells acclimated to low growth salinities (hyposaline stress, i.e. < 0.2 mol/L NaCl) showed major increases in glutathione and alpha-tocopherol coupled with decreases in Fv/Fm ratios and in total and reduced ascorbate compared to moderate and high external salinities. Cell volumes remained unchanged, except at the lowest salinity where they doubled. Catalase, superoxide dismutase, dehydroascorbate reductase and glutathione reductase activities were not altered by extreme salinities. The involvement of oxidative stress at both salinity extremes is implied by the alterations in antioxidant enzymes and substrates, but the specific changes are very different between hypo and hypersaline stresses.

Ascorbate Peroxidases↗
PubMed2006

Overexpressing a NAM, ATAF, and CUC (NAC) transcription factor enhances drought resistance and salt tolerance in rice.

Drought and salinity are major abiotic stresses to crop production. Here, we show that overexpression of stress responsive gene SNAC1 (STRESS-RESPONSIVE NAC 1) significantly enhances drought resistance in transgenic rice (22-34% higher seed setting than control) in the field under severe drought stress conditions at the reproductive stage while showing no phenotypic changes or yield penalty. The transgenic rice also shows significantly improved drought resistance and salt tolerance at the vegetative stage. Compared with WT, the transgenic rice are more sensitive to abscisic acid and lose water more slowly by closing more stomatal pores, yet display no significant difference in the rate of photosynthesis. SNAC1 is induced predominantly in guard cells by drought and encodes a NAM, ATAF, and CUC (NAC) transcription factor with transactivation activity. DNA chip analysis revealed that a large number of stress-related genes were up-regulated in the SNAC1-overexpressing rice plants. Our data suggest that SNAC1 holds promising utility in improving drought and salinity tolerance in rice.

Abscisic Acid↗
PubMed2004

Concomitant airway expression of granulocyte-macrophage colony-stimulating factor and decorin, a natural inhibitor of transforming growth factor-beta, breaks established inhalation tolerance.

We previously showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) breaks tolerance induction. The objective of this study was to determine whether GM-CSF breaks established inhalation tolerance. To induce tolerance, BALB/c mice were exposed to aerosolized ovalbumin (OVA) for 10 consecutive days. A control group was exposed to saline. Subsequently, tolerant and control animals were exposed to OVA in a GM-CSF-enriched airway microenvironment. Tolerant animals, unlike control animals, did not develop airway and peripheral blood eosinophilia, had diminished levels of OVA-specific IgE, and reduced airway hyper-responsiveness. While tolerant animals did not express IL-4, IL-5 and IL-13, levels of the regulatory cytokines IL-10, IFN-gamma and transfoming growth factor (TGF)-beta were similar between tolerant and non-tolerant animals. Lung CD4+ T cells were activated according to CD69, CD25 and T1/ST2 expression, but systemic responses characterized by splenocyte proliferation and Th2 effector function were dramatically reduced. Concurrent expression of GM-CSF and decorin, a natural inhibitor of TGF-beta, reversed eosinophilic unresponsiveness. Our study suggests that the breakdown of tolerance and, by extension, the emergence of eosinophilic inflammation, requires two signals: one that triggers sensitization and one that interferes with negative regulation. Moreover, our study shows that dysregulated expression of an extracellular matrix protein may break established tolerance and lead to eosinophilic airway inflammation.

Administration, Inhalation↗