Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peritoneal leucocytosis, with an increased percentage of eosinophils, was found in mice which had been infected with Schistosoma mansoni for 7 weeks or longer. Specific IgG against worm and egg antigens increased in peritoneal fluids and their corresponding sera respectively 5 and 7 weeks after infection. An intraperitoneal challenge with schistosomula elicited neutrophilia in all mice regardless of immune status, as well as infiltration of eosinophils and macrophages in infected mice. The secondary eosinophilia occurred in mice previously infected for 1 week or longer, whereas the infiltration of macrophages occurred only after worms from the primary infection had started laying eggs. Unlike the eosinophilia the macrophage response required infection with bisexual populations of cercariae. Injection of previously infected mice with Escherichia, Trichinella or Toxocara failed to increase the proportions of eosinophils and macrophages. Schistosomula-induced eosinophilia could be elicited in passively sensitized mice. Intraperitoneal injection of PBS extract of adult worms elicited eosinophilia in infected mice and neutrophilia in normal mice. Two chromatographic fractions induced eosinophilia and the third only neutrophilia. The relevance of these observations to host response to S. mansoni infections is discussed.
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PMID:An in vivo model for the study of chemotaxis induced by schistosomula of Schistosoma mansoni. 308 92

Inflammatory cell infiltrates and cell adhesion molecule expression have been examined in normal human skin after intradermal injection of sensory neuropeptides substance P (n = 6), vasoactive intestinal polypeptide (n = 6), and calcitonin gene-related peptide (n = 6) together with PBS as control (n = 4). Each neuropeptide induced rapid, time-dependent neutrophil influx into dermis, which was initially observed at 15 min and persisted for 8 h after injection. Increases in numbers of neutrophils with time after substance P, vasoactive intestinal polypeptide and calcitonin gene-related peptide were highly significant when compared with controls p < 0.005, p < 0.005, p < 0.005, respectively (analysis of variance). Substance P additionally induced marked eosinophilic accumulation at 4 and 8 h in four of six subjects. These changes paralleled rapid translocation of P-selectin from cytoplasmic Weibel-Palade granules to luminal membranes by 15 min, and significant up-regulation of E-selectin expression at 4 and 8 h. Increases in percentage of E-selectin positive vessels with respect to time after each neuropeptide were highly significant when compared with controls, p < 0.005, p < 0.005, p < 0.005 (ANOVA), respectively, and were significantly correlated with neutrophil infiltrates, r = 0.55, p < 0.001. VCAM-1 was not expressed, and constitutive ICAM-1 expression on dermal endothelium was unchanged at all time points examined (0-8 h). Induction of endothelial adhesion molecule expression by neuropeptides provides a mechanism for neutrophil accumulation in neurogenic inflammation. Substance P-induced eosinophil accumulation in the absence of VCAM-1 expression suggests that mechanisms distinct from VCAM-1/very late antigen-4 binding mediate selective tissue eosinophilia.
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PMID:Neuropeptides induce rapid expression of endothelial cell adhesion molecules and elicit granulocytic infiltration in human skin. 769 Aug

We investigated the effects of IL-12 on a murine model of allergic lung inflammation. Administration of IL-12 was timed to interfere with either allergic sensitization (early dosage) or the hypersensitivity inflammatory response in the lung (late dosage), or both (early and late dosages). Comparisons of IL-12- and PBS-treated animals within each treatment group revealed several noticeable effects of IL-12. Early dosage, and the combination of early and late dosages, strikingly decreased ragweed-specific serum IgE, tracheal ring reactivity to acetylcholine, and BAL eosinophilia following allergen challenge. In contrast, late dosage had no effect on IgE levels and only a minimal effect on tracheal ring reactivity, but had a modest effect on recruitment of eosinophils. Early dosage down-regulated IL-5 and IL-10, but did not alter IL-4 or IFN-gamma expression. Late dosage down-regulated IL-5, up-regulated IL-10 and IFN-gamma, but did not change IL-4 expression. The combination of early and late dosage down-regulated IL-4, IL-5, and IL-10 expression, but increased IFN-gamma expression and production in the BAL cells and fluids. Taken together, these results indicate that IL-12 has potent immunomodulatory effects on allergic lung inflammation that depend on the timing of IL-12 administration relative to allergic sensitization and allergen challenge.
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PMID:Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses. 889 55

The cysteinyl leukotriene LTE4 has been shown to induce airway eosinophilia in asthmatics in vivo. This phenomenon has not yet been reported for LTD4. Hence, we examined the effect of inhaled LTD4 and a control bronchoconstrictor agent, methacholine, on cell differentials in hypertonic saline-induced whole sputum samples of 12 nonsmoking atopic asthmatic subjects (three women, nine men; 21 to 29 yr of age; FEV1, 74 to 120% pred; PC20FEV1 methacholine < 9.6 mg/ml). The study had a cross-over, placebo-controlled design consisting of 4 d separated by > or = 1 wk. On each randomized study day, the subjects inhaled five serial doses of either LTD4 (mean cumulative concentration: 95.7 microM) or methacholine (mean cumulative concentration: 542 mM) or five doses of their respective diluents (PBS/ethanol or PBS). The airway response was measured by FEV1, followed by sputum induction with 4.5% NaCl, 4 h postchallenge. Inflammatory cells (> or = 250) were counted twice on coded cytospins and expressed as percentages of nonsquamous cells. There was no significant difference in the maximal percent fall in FEV1 from baseline between LTD4 (mean +/- SEM, 49.5 +/- 4.4% fall) and methacholine (mean +/- SEM, 55.9 +/- 3.4% fall) (p = 0.11). LTD4 induced a significant increase in the percentage of sputum eosinophils as compared with its diluent (mean +/- SD, 26.6 +/- 21.3% and 10.2 +/- 8.8%, respectively; p = 0.025), whereas a similar trend for methacholine failed to reach significance (mean +/- SD, 19.1 +/- 22.9% and 7.8 +/- 5.8%, respectively; p = 0.11). There was no significant difference in the changes in the percentage of sputum eosinophils between LTD4 and methacholine (mean difference +/- SD, 7.5 +/- 12.5% eosinophils; p = 0.09). We conclude that LTD4 induces eosinophilia in sputum of asthmatic subjects 4 h after inhalation. Our data suggest that LTD4 recruits eosinophils into the airways of asthmatics in vivo, possibly by virtue of direct or indirect chemotactic properties, whereas an additional effect of vigourous airway narrowing per se cannot be excluded.
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PMID:The effect of inhaled leukotriene D4 and methacholine on sputum cell differentials in asthma. 910 62

Allergic asthma is thought to be mediated by CD4+ T lymphocytes producing the Th2-associated cytokines, IL-4, and IL-5. Recently, the costimulatory molecules B7-1 and B7-2, which are expressed on the surface of APC, have been suggested to influence the development of Th1 vs Th2 immune responses. We examined the in vivo role of these costimulatory molecules in the pathogenesis of Th2-mediated allergen-induced airway hyperresponsiveness in a murine model of asthma. In this model, OVA-sensitized A/J mice develop significant increases in airway responsiveness, pulmonary eosinophilia, and pulmonary Th2 cytokine expression following aspiration challenge with OVA as compared with PBS-control animals. Strikingly, administration of anti-B7-2 mAb to OVA-treated mice abolished allergen-induced airway hyperresponsiveness, pulmonary eosinophilia, and elevations in serum IgG1 and IgE levels. Anti-B7-2 treatment of OVA-treated mice reduced both total lung IL-4 and IL-5 mRNA and bronchoalveolar lavage fluid IL-4 and IL-5 protein levels, with no significant changes in IFN-gamma message or protein levels. In contrast, treatment with anti-B7-1 mAbs had no effect on allergen-induced airway hyperresponsiveness, IgE production, or cytokine production, however, it significantly suppressed pulmonary eosinophilia. We conclude that B7-2 provides the necessary costimulatory signal required for the development of in vivo allergic responses to inhaled allergen exposure.
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PMID:Development of murine allergic asthma is dependent upon B7-2 costimulation. 955 45

Asthma and its exacerbation by air pollution are major public health problems. This investigation sought to more precisely model this disorder, which primarily affects children, by using very young mice. The study first attempted to create allergic airway hypersensitivity in neonatal mice and to determine if physiologic testing of airway function was possible in these small animals. Neonatal mice were sensitized by i.p. injection of ovalbumin (OVA, 5 microg) and alum (1 mg) at 3 and 7 d of age. One week later, mice were challenged by allergen nebulization (3% OVA in PBS, 10 min/d, d 14-16). OVA-exposed mice showed: (1) increased airway hyperresponsiveness (AHR) to methacholine by whole-body plethysmography; (2) eosinophilia in bronchoalveolar lavage (BAL) fluid; (3) airway inflammation using histopathology techniques; and (4) elevated serum anti-OVA immunoglobulin E. Hence, these neonatal mice were successfully sensitized and manifested "asthmatic" responses after allergen challenge. Experiments were conducted to investigate the effect of one surrogate for ambient air particles, residual oil fly ash (ROFA), on this juvenile asthma model. Aerosolized ROFA leachate (supernatant of 50 mg/ml, 30 min, on d 15) had no marked effect alone, but caused a significant increase in AHR and airway inflammation in OVA-sensitized and challenged mice. This synergistic effect was abrogated by the antioxidant dimethylthiourea (DMTU, 3 mg/kg mouse, i.p.). This model may be useful to study air pollution-mediated exacerbation of asthma in children.
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PMID:Increased airway hyperresponsiveness and inflammation in a juvenile mouse model of asthma exposed to air-pollutant aerosol. 1052 45

To test the hypothesis that CD8+ T cells may suppress the allergen-induced late airway response (LAR) and airway eosinophilia, we examined the effect of administration of Ag-primed CD8+ T cells on allergic airway responses, bronchoalveolar lavage (BAL) leukocytes, and mRNA expression for cytokines (IL-4, IL-5, and IFN-gamma) in OVA-sensitized Brown Norway rats. On day 12 postsensitization to OVA, test rats were administered 2 million CD8+ T cells i.p. isolated from either the cervical lymph nodes (LN group; n = 8) or the spleen (Spl group; n = 6) of sensitized donors. On day 14, test rats were challenged with aerosolized OVA. Control rats were administered PBS i.p. on day 12, and challenged with OVA (n = 10) or BSA (n = 6) on day 14. The lung resistance was measured for 8 h after challenge. BAL was performed at 8 h. Cytospin slides of BAL were analyzed for major basic protein by immunostaining and for cytokine mRNA by in situ hybridization. The LAR was significantly less in the LN group (1.8 +/- 0.5 U; p < 0.01) and BSA controls (1.4 +/- 0.7; p < 0.01), but not in the Spl group (6.7 +/- 2.2), compared with that in OVA controls (8.1 +/- 1.8). In BAL, the number of major basic protein-positive cells was lower in the LN and Spl groups compared with OVA controls (p < 0.05 and p < 0.01). IL-4- and IL-5-positive cells were decreased in the LN group compared with the OVA controls (p < 0.01). INF-gamma-positive cells were increased in the LN and Spl groups compared with the OVA controls (p < 0.01). Serum OVA-specific IgE levels were unaffected by CD8+ T cell transfers. These results indicate that Ag-primed CD8+ T cells have a potent suppressive effect on LAR.
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PMID:CD8+ T cells modulate late allergic airway responses in Brown Norway rats. 1055 86

The effects of recombinant interleukin-12 (rIL-12) on immune responses generated by subunit vaccines for respiratory syncytial virus (RSV) were evaluated in BALB/c mice. Parenteral co-administration of rIL-12 with F/AlOH or F/PBS resulted in accelerated clearance of infectious virus from the lungs 4 days after challenge. The immune responses elicited by 0.03 microg of F protein plus 10 ng of rIL-12 adsorbed to AlOH were more efficacious than those induced by 3 microg of F protein co-formulated with 1,000 ng of rIL-12 in PBS alone. Adsorption to AIOH prolonged the presence of rIL-12 in the sera. The resultant systemic humoral immune responses after vaccination with F/AlOH or G/AlOH were dependent on the dose of rIL-12 and characterized by heightened serum immunoglobulin G2a (IgG2a) antibody titers. Co-administration of rIL-12 with F/AlOH was also associated with diminished protein-specific IgE titers, elevated neutralizing antibody titers, and interferon-gamma and (IFN-gamma) in the sera, and enhanced antigen-dependent killer cell activity in the lungs after challenge. For maximum benefit, the data suggested that rIL-12 must be co-administered with F/AlOH. Collectively, the results indicated that rIL-12 directed immune responses toward a type 1 phenotype. However, examination of pulmonary inflammatory cells after challenge suggested that the type 1 phenotype was not absolute. Co-formulation with rIL-12 did not diminish pulmonary eosinophilia upon challenge of naive mice primed with F/AlOH, G/AlOH, or FI-RSV, and CD4+ T cells were expanded relative to the CD8+ T-cell compartment. These results are important for the future design of subunit vaccines against RSV.
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PMID:The immunogenicity of subunit vaccines for respiratory syncytial virus after co-formulation with aluminum hydroxide adjuvant and recombinant interleukin-12. 1073 69

Monocyte chemoattractant proteins-1 and -5 have been implicated as important mediators of allergic pulmonary inflammation in murine models of asthma. The only identified receptor for these two chemokines to date is the CCR2. To study the role of CCR2 in a murine model of Ag-induced asthma, we compared the pathologic and physiological responses of CCR2(-/-) mice with those of wild-type (WT) littermates following immunization and challenge with OVA. OVA-immunized/OVA-challenged (OVA/OVA) WT and CCR2(-/-) mice developed significant increases in total cells recovered by bronchoalveolar lavage (BAL) compared with their respective OVA-immunized/PBS-challenged (OVA/PBS) control groups. There were no significant differences in BAL cell counts and differentials (i.e., macrophages, PMNs, lymphocytes, and eosinophils) between OVA/OVA WT and CCR2(-/-) mice. Serologic evaluation revealed no significant difference in total IgE and OVA-specific IgE between OVA/OVA WT mice and CCR2(-/-) mice. Lung mRNA expression and BAL cytokine protein levels of IL-4, IL-5, and IFN-gamma were also similar in WT and CCR2(-/-) mice. Finally, OVA/OVA CCR2(-/-) mice developed increased airway hyper-responsiveness to a degree similar to that in WT mice. We conclude that following repeated airway challenges with Ag in sensitized mice, the development of Th2 responses (elevated IgE, pulmonary eosinophilia, and lung cytokine levels of IL-4 and IL5) and the development of airway hyper-responsiveness are not diminished by a deficiency in CCR2.
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PMID:CC chemokine receptor-2 is not essential for the development of antigen-induced pulmonary eosinophilia and airway hyperresponsiveness. 1108

An alkali-insoluble fraction 1 (F1), which contains mainly ss-glucan isolated from the cell wall of Histoplasma capsulatum, induces eosinophil recruitment into the peritoneal cavity of mice. The present study was carried out to determine the participation of interleukin-5 (IL-5) in this process. Inbred C57BL/6 male mice weighing 15-20 g were treated ip with 100 microg of anti-IL-5 monoclonal antibody (TRFK-5, N=7) or an isotype-matched antibody (N=7), followed by 300 microg F1 in 1 ml PBS ip 24 h later. Controls (N=5) received only 1 ml PBS. Two days later, cells from the peritoneal cavity were harvested by injection of 3 ml PBS and total cell counts were determined using diluting fluid in a Neubauer chamber. Differential counts were performed using Rosenfeld-stained cytospin preparations. The F1 injection induced significant (P<0.01) leukocyte recruitment into the peritoneal cavity (8.4 x 10(6) cells/ml) when compared with PBS alone (5.5 x 10(6) cells/ml). Moreover, F1 selectively (P<0.01) induced eosinophil recruitment (1 x 10(6) cells/ml) when compared to the control group (0.07 x 10(6) cells/ml). Treatment with TRFK-5 significantly (P<0.01) inhibited eosinophil recruitment (0.18 x 10(6) cells/ml) by F1 without affecting recruitment of mononuclear cells or neutrophils. We conclude that the F1 fraction of the cell wall of H. capsulatum induces peritoneal eosinophilia by an IL-5-dependent mechanism. Depletion of this cytokine does not have effect on the recruitment of other cell types induced by F1.
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PMID:Interleukin-5 mediates peritoneal eosinophilia induced by the F1 cell wall fraction of Histoplasma capsulatum. 1506 Jul 1


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