Objective and design: We examined the reversibility of several changes in the lungs and airways of mice immediately after exposure to ovalbumin aerosol and after a period of recovery breathing clean air.Methods: Mice were exposed for 1, 2, 4, 6, 8, or 10 weeks, with recovery in clean air for 1–3 weeks.Results: Airway collagen content, exhaled NO, airway mucous cell hyperplasia, and lung lavage inflammatory cell content increased upon exposure to ovalbumin aerosol. All parameters except airway fibrosis decreased partially or completely to control values with recovery in clean air.Conclusions: Airway mucous cell hypertrophy and hyperplasia appear to be completely reversible after recovery in clean air, while exhaled NO and airway inflammation appear to be mostly reversible, except for persistence of lymphocytes in the lung lavage fluid. Airway fibrosis appears to be reversible when mice are exposed to ovalbumin aerosol for periods of up to 4 weeks of exposure, but becomes irreversible after 6 or more weeks of exposure.Received 30 June 2004; returned for revision 24 September 2004; accepted by J. S. Skotnicki 13 October 2004 相似文献
In this article we present a patient with acute lymphoblastic leukemia (ALL) associated with eosinophilia, in which the eosinophilia preceded a meningeal and bone-marrow relapse of ALL. We analysed the purine and pyrimidine nucleotide content of the eosinophils (92% pure) and compared the nucleotide pattern with that of eosinophils from healthy donors and from patients with eosinophilia not associated with leukemia. The ratios of purine : pyrimidine and of uracil :cytosine nucleotides were decreased compared with those in eosinophils from healthy donors and from patients with eosinophilia with other aetiologies. The total nucleotide concentration was increased, especially the concentration of UDP-sugars and pyrimidine nucleotides.
The decrease in these ratios and the increase in concentration of the nucleotides and the UDPsugars were also detected in leukemic cells of patients with ALL (de Korte et al., Leukemia Res. 10, 389–396 (1986)) compared to normal lymphocytes. We suggest a malignant character of the eosinophils in our patient with ALL associated with eosinophilia, in contrast with the nonmalignant state suggested previously for these cells. 相似文献
The pathways conferring immunity to human filariases are not well known, in part because human-pathogenic filariae do not
complete a full life cycle in laboratory mice. We have used the only fully permissive infection of mice with filariae, i.e.,
infection of BALB/c mice with the rodent filarial nematode Litomosoides sigmodontis. Our previous results showed that worm development is inversely correlated with Th2 cytokine production and eosinophilia.
The scope of the present study was to directly elucidate the role of interleukin-5 (IL-5) and eosinophils in controlling the
development of L. sigmodontis after vaccination and in primary infection. BALB/c mice immunized with irradiated third-stage larvae (L3) were confirmed
to have elevated IL-5 levels as well as high subcutaneous eosinophilia and to attack and reduce incoming larvae within the
first 2 days, resulting in 70% reduction of worm load. Treatment of vaccinated mice with anti-IL-5 antibody (TRFK-5) suppressed
both blood and tissue eosinophilia and completely abolished protection. This demonstrates, for the first time in a fully permissive
filarial infection, that IL-5 is essential for protection induced by irradiated L3 larvae. In contrast, in primary-infected
mice, anti-IL-5 treatment did not modify filarial infection within the 1st month, most likely because during primary infection
IL-5-dependent mechanisms such as subcutaneous eosinophilia are induced too late to disturb worm establishment. However, there
is a role for IL-5 late in primary infection where neutrophil-dependent worm encapsulation is also under the control of IL-5.
Received: 30 March 2000 相似文献
The pathogenesis of human asthma and the development of key features of pulmonary allergy in mouse models has been critically linked to IL-13. Analyses of the receptor components employed by IL-13 have shown that delivery of this cytokine to the airways of naive IL-4Ralpha gene targeted (IL-4Ralpha(-/-)) mice fails to induce disease, suggesting that this membrane protein is critical for transducing IL-13-mediated responses. The current study demonstrates that, in contrast to naive mice, T helper 2 bias, airways hyperreactivity (AHR) and tissue eosinophilia develop in Ovalbumin-sensitized IL-4Ralpha(-/-) mice and that these responses can be inhibited by the IL-13 antagonist sIL-13Ralpha2Fc. Therefore, antigen stimulation induces an IL-13-regulated response that is independent of IL-4Ralpha. To determine the role of IL-5 and eosinophils in the development of disease in antigen-exposed IL-4Ralpha(-/-) mice, pulmonary allergy was examined in mice deficient in both factors. IL-4Ralpha/IL-5(-/-) mice were significantly defective in their ability to produce IL-13 and failed to develop AHR, suggesting that IL-5 indirectly regulates AHR in allergic IL-4Ralpha(-/-) mice by an IL-13-dependent mechanism. Collectively, these results demonstrate that IL-13-dependent processes regulating the development of AHR and T helper bias persist in the in the lungs of allergic IL-4Ralpha(-/-) mice. 相似文献
Helicobacter pylori (Hp) colonizes the human gastric mucosa with a high worldwide prevalence. Currently, Hp can be eradicated by the use of antibiotics. Due to the increase of antibiotic resistance, new therapeutic strategies need to be devised: one such approach being prophylactic vaccination. Pre-clinical and clinical data showed that a urease-based vaccine is efficient in decreasing Hp infection through the mobilization of T helper (Th)-dependent immune effectors, including eosinophils. Preliminary data have shown that upon vaccination and subsequent Hp infection, eosinophils accumulate in the gastric mucosa, suggesting a possible implication of this granulocyte subset in the vaccine-induced reduction of Hp infection.In our study, we confirm that activated eosinophils, expressing CD63, CD40, MHCII and PD-L1 at their cell surface, infiltrate the gastric mucosa during vaccine-induced reduction of Hp infection. Strikingly, we provide evidence that bone marrow derived eosinophils efficiently kill Hp in vitro, suggesting that eosinophils may participate to the vaccine-induced reduction of Hp infection. However, conversely to our expectations, the absence of eosinophils does not decrease the efficacy of this Hp vaccine in vivo. Indeed, vaccinated mice that have been genetically ablated of the eosinophil lineage or that have received anti-Sialic acid-binding immunoglobulin-like lectin F eosinophil-depleting antibodies, display a lower Hp colonization when compared to their eosinophil sufficient counterparts. Although the vaccine induces similar urease-specific humoral and Th responses in both eosinophil sufficient and deficient mice, a decreased production of anti-inflammatory cytokines, such as IL-10, TGFβ, and calgranulin B, was specifically observed in eosinophil depleted mice.Taken together, our results suggest that gastric eosinophils maintain an anti-inflammatory environment, thus sustaining chronic Hp infection. Because eosinophils are one of the main immune effectors mobilized by Th2 responses, our study strongly suggests that the formulation of an Hp vaccine needs to include an adjuvant that preferentially primes Hp-specific Th1/Th17 responses. 相似文献
Objective: Asthma is a common heterogeneous disease characterized by airway inflammation and bronchoconstriction. Current treatment guidelines provide recommendations for categorizing disease severity, asthma control and management. This paper reviews asthma assessment in primary care and describes the pathophysiology, clinical characteristics and new targeted treatments available for patients with severe eosinophilic asthma.
Methods: A non-systematic PubMed literature search was conducted and articles, primarily from the last 5?years, were selected based on relevance to primary care practice, asthma pathophysiology and biologic therapies.
Results: Despite optimal therapy including high-dose inhaled corticosteroids (ICS), long-acting β2-agonists and tiotropium, ~4–10% of all patients with severe asthma continue to have poor asthma control. These patients have impaired quality of life, frequent exacerbations and are exposed to the side effects of repeated courses of oral steroids. Approximately 50% of patients with severe uncontrolled asthma have eosinophilic asthma, with increased airway expression of type 2 cytokines IL-4, IL-5 and IL-13. Eosinophilic asthma is identified in primary care by having eosinophils ≥150–300 cells/μL on a complete blood count with differential.
Conclusions: A new class of agents is available for patients with moderate to severe eosinophilic asthma. Four biologic therapies – mepolizumab, reslizumab, benralizumab and dupilumab – that interfere with the regulation and activity of eosinophils have been approved by the FDA for patients with moderate to severe asthma with an eosinophilic phenotype. Primary care physicians should be familiar with these medications to explain part of the rationale for referral to specialist care and manage patient expectations for treatment. 相似文献