Interleukin-5 Modulates Eosinophil Accumulation in Allergic Guinea Pig Lung

Gulbenkian, A.; Egan, Robert W.; Fernandez, Xiomara; Jones, Howard; Kreutner, William; Kung, Ted T.; Payvandi, Faribourz; Sullivan, L.; Zurcher, Jackie; Watnick, Arthur S.

doi:10.1164/ajrccm/146.1.263

Cited by 135 publications

(76 citation statements)

References 11 publications

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“…It is possible that increased serum level of IL-5 may originate from several tissues, including lungs, local lymph nodes, and bone marrow. However, the exact site of action of anti-IL-5 on allergen-induced airway eosinophilia has not been clearly described in several previous studies in which anti-IL-5 was administered systemically (27)(28)(29)(30)(31)(32). A recent study has shown that the anti-IL-5 Ab delivered via the airway route attenuates allergen-induced eosinophilia in BAL and lung tissues (47).…”

Section: Discussionmentioning

confidence: 99%

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

Tomaki

Zhao

Lundahl

et al. 2000

The Journal of Immunology

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The airway inflammation in asthma is dominated by eosinophils. The aim of this study was to elucidate the contribution of newly produced eosinophils in airway allergic inflammation and to determine mechanisms of any enhanced eosinophilopoiesis. OVA-sensitized BALB/c mice were repeatedly exposed to allergen via airway route. Newly produced cells were identified using a thymidine analog, 5-bromo-2′-deoxyuridine, which is incorporated into DNA during mitosis. Identification of IL-5-producing cells in the bone marrow was performed using FACS. Bone marrow CD3+ cells were enriched to evaluate IL-5-protein release in vitro. Anti-IL-5-treatment (TRFK-5) was given either systemically or directly to the airways. IL-5R-bearing cells were localized by immunocytochemistry. Repeated airway allergen exposure caused prominent airway eosinophilia after three to five exposures, and increased the number of immature eosinophils in the bone marrow. Up to 78% of bronchoalveolar lavage (BAL) granulocytes were 5-bromo-2′-deoxyuridine positive. After three allergen exposures, both CD3+ and non-CD3 cells acquired from the bone marrow expressed and released IL-5-protein. Anti-IL-5 given i.p. inhibited both bone marrow and airway eosinophilia. Intranasal administration of anti-IL-5 also reduced BAL eosinophilia, partly via local effects in the airways. Bone marrow cells, but not BAL eosinophils, displayed stainable amounts of the IL-5R α-chain. We conclude that the bone marrow is activated by airway allergen exposure, and that newly produced eosinophils contribute to a substantial degree to the airway eosinophilia induced by allergen. Airway allergen exposure increases the number of cells expressing IL-5-protein in the bone marrow. The bone marrow, as well as the lung, are possible targets for anti-IL-5-treatment.

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Section: Discussionmentioning

confidence: 99%

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

Tomaki

Zhao

Lundahl

et al. 2000

The Journal of Immunology

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“…The first class, in this study termed type I, is exemplified by chicken egg OVA which, aside from airway hyperresponsiveness (1), is incapable of inducing a broad spectrum of lung allergic changes which additionally include goblet cell metaplasia, mucus oversecretion, airway eosinophilia, and peribronchovascular inflammation, if given strictly by inhalation. However, OVA is capable of inducing all of these allergic changes if given remote from the lung in a series of priming doses, typically with aluminum-based adjuvants before intrapulmonary challenge (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). In contrast, the other major class of allergen, in this study termed type II, is derived from the fungus Aspergillus fumigatus and readily induces allergic lung inflammation when given only through the airway and without the need for additional adjuvant (12)(13)(14).…”

Section: Efining the Immunopathologic Basis Of Allergic Inflam-mentioning

confidence: 99%

A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease

Kheradmand

Kiss

et al. 2002

The Journal of Immunology

290

292

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The respiratory allergens that induce experimental Th cell type 2-dependent allergic lung inflammation may be grouped into two functional classes. One class of allergens, in this study termed type I, requires priming with adjuvants remote from the lung to overcome airway tolerogenic mechanisms that ordinarily preclude allergic responses to inhaled Ags. In contrast, the other, or type II, allergen class requires neither remote priming nor additional adjuvants to overcome airway tolerance and elicit robust allergic lung disease. In this study, we show in an experimental model that diverse type II allergens share in common proteolytic activity that is both necessary and sufficient for overcoming airway tolerance and induction of pulmonary allergic disease. Inactivated protease and protease-free Ag fragments showed no allergenic potency, demonstrating that only active protease acting on endogenous substrates was essential. Furthermore, induction of airway tolerance could be aborted and allergic lung disease established by simply adding purified protease to a type I allergen. Thus, exogenous proteases are common to type II allergens and may be generally required to overcome the innate resistance of the airway to Th cell type 2 activation and allergic inflammation, raising concern for their potential contribution to diseases such as asthma.

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“…IL-5 administration has been shown to increases mucosal exudation, enhance eosinophil recruitment into the lungs and to increases airways responsiveness in models of allergen induced BHR in the guinea pig (Gulbenkian et al 1992, van Oosterhout et al 1993a, in mice (van Oosterhout et al 1993b), and in the Brown Norway rat (Renzi et al 1996). Moreover, anti-IL-5 administration inhibits eosinophil recruitment and airways hyperresponsiveness in guinea pig models of allergic pulmonary inflammation and allergen induced BHR (Gulbenkian et al 1992, van Oosterhout et al 1993a, Das et al 1995. Similar findings have also been demonstrated in the the mouse (Nagai et al 1993 and in the monkey .…”

Section: Il-5 and Anti-il-5 Administrationmentioning

confidence: 99%

IL-5 and IL-5 receptor in asthma

Kotsimbos

Hamid

1997

Mem. Inst. Oswaldo Cruz

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and a soluble isoform (αIL-5Rs). Cytokines such as IL-5 produce specific and non-specific cellular responses through specific cell membrane receptor mediated activation of intracellular signal transduction pathways which, to a large part, regulate gene expression. The major intracellular signal transduction mechanism is activation of non-receptor associated tyrosine kinases including JAK and MAP kinases which can then transduce signals via a novel family of transcriptional factors named signal transducers and activators of transcription (STATS). JAK2, STAT1 and STAT 5 appear to be particularly important in IL-5 mediated eosinophil responses. Asthma is characterized by episodic airways obstruction, increased bronchial responsiveness, and airway inflammation. Several studies have shown an association between the number of activated T cells and eosinophils in the airways and abnormalities in FEV1, airway reactivity and clinical severity in asthma. It has now been well documented that IL-5 is highly expressed in the bronchial mucosa of atopic and intrinsic asthmatics and that the increased IL-5 mRNA present in airway tissues is predominantly T cell derived. Immunocytochemical staining of bronchial biopsy sections has confirmed that IL-5 mRNA transcripts are translated into protein in asthmatic subjects. Furthermore, the number of activated CD 4 + T cells and IL-5 mRNA positive cells are increased in asthmatic airways following antigen challenge and studies that have examined IL-5 expression in asthmatic subjects before and after steroids have shown significantly decreased expression following oral corticosteroid treatment in steroid-sensitive asthma but not in steroid resistant and chronic severe steroid dependent asthma. The link between T cell derived IL-5 and eosinophil activation in asthmatic airways is further strengthened by the demonstration that there is an increased number of αIL-5R mRNA positive cells in the bronchial biopsies of atopic and non-atopic asthmatic subjects and that the eosinophil is the predominant site of this increased

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Interleukin-5 Modulates Eosinophil Accumulation in Allergic Guinea Pig Lung

Cited by 135 publications

References 11 publications

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease

IL-5 and IL-5 receptor in asthma

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