T Lymphocytes and Eosinophils in Allergen-induced Late-phase Asthmatic Reactions in the Guinea Pig

Frew, Anthony J.; Moqbel, Redwan; Azzawi, May; Hartnell, Adele; Barkans, J.; Jeffery, Peter K.; Kay, A. B.; Scheper, Rik J.; Varley, J. G.; Church, Martin K.; Holgate, Stephen T.

doi:10.1164/ajrccm/141.2.407

Cited by 115 publications

(45 citation statements)

References 7 publications

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“…However, FREW et al [42] used immunocytochemical techniques to demonstrate a rise in Tlymphocyte numbers in the airway wall after challenge. This influx was not reflected by an increase in the numbers of T-cells in BALF, suggesting that these cells infiltrate the mucosa but may not migrate to the airway lumen in this species.…”

Section: Discussionmentioning

confidence: 99%

Time-course of antigen-induced airway inflammation in the guinea-pig and its relationship to airway hyperresponsiveness

Underwood¹,

Foster²,

Raeburn³

et al. 1995

Eur Respir J

100

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The causative relationship between airway inflammation and hyperreactivity is unclear, since inflammatory changes have been examined at one or, at most, a few time-points after antigen challenge in both human asthma and animal models. We have made a detailed investigation of inflammatory and functional changes in the airways up to 8 days after antigen challenge in guinea-pigs. In particular, we examined the hypothesis that eosinophil-derived mediators contribute to tissue damage and the development of airway hyperresponsiveness.Following antigen challenge, the influx of inflammatory cells and mediator release in airway tissue and bronchoalveolar lavage fluid were correlated temporally with histopathological changes in airway tissue and airway responsiveness.Eosinophil influx was demonstrable at 4 h. Eosinophilia peaked after 24 h and persisted for at least 8 days. Parallel increases in the concentrations of major basic protein and eosinophil cationic protein in bronchoalveolar lavage fluid indicated that the eosinophils were activated. Eosinophilia was accompanied by subepithelial oedema and epithelial damage co-localized with major basic protein immunoreactivity. A transient neutrophilia (<48 h duration) and an increase in neutrophil elastase in bronchoalveolar lavage fluid peaked at 14 h. The proportion of airway macrophages with an activated morphology increased at 8 h and remained markedly elevated until 72 h. Airways were hyperresponsive to histamine at 4 h and for at least 8 days.The antigen-induced airway inflammation resemble in time-course and histopathology that seen in antigen-challenged asthmatics, and indicate that the eosinophil and its cytotoxic proteins may be major mediators of airway mucosal damage and airway hyperresponsiveness.

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Section: Discussionmentioning

confidence: 99%

Time-course of antigen-induced airway inflammation in the guinea-pig and its relationship to airway hyperresponsiveness

Underwood¹,

Foster²,

Raeburn³

et al. 1995

Eur Respir J

100

View full text Add to dashboard Cite

show abstract

“…There is evidence that T cells are recruited into the airways during allergic responses in humans (8) and animals (9). However, compared to neutrophils and eosinophils, both of which have been postulated to be important mediators of the LAR ( 10,11), lymphocytes have not been directly implicated in the bronchoconstriction that accompanies the LAR.…”

Section: Introductionmentioning

confidence: 99%

Transfer of allergic airway responses with antigen-primed CD4+ but not CD8+ T cells in brown Norway rats.

Watanabe

Mishima²,

Renzi³

et al. 1995

J. Clin. Invest.

122

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Activated CD4+ helper T cells have been demonstrated in asthmatic airways and postulated to play a central role in eliciting allergic inflammation; direct evidence of their involvement seems to be lacking. We hypothesized that CD4+ T cells have the potential to induce allergic responses to antigen challenge, and tested this hypothesis in a model of allergic bronchoconstriction, the Brown Norway rat, using the approach of adoptive transfer. Animals were actively sensitized to either ovalbumin (OVA) or BSA and were used as donors of T cells. W3/25 (CD4) + or OX8 (CD8) + T cells were isolated from the cervical lymph nodes of sensitized donors and transferred to naive BN rats. 2 d after adoptive transfer recipient rats were challenged by OVA inhalation, and changes in lung resistance (RL), bronchoalveolar lavage (BAL) cells, and serum levels of antigen-specific IgE were studied. After OVA challenge recipients of OVA-primed W3/25+ T cells exhibited sustained increases in RL throughout the entire 8-h observation period and had significant bronchoalveolar lavage eosinophilia, which was detected by immunocytochemistry using an antimajor basic protein mAb. Recipients of BSA-primed W3/25+ T cells or OVAprimed OX8+ T cells failed to respond to inhaled OVA. OVA-specific immunoglobulin E was undetectable by ELISA or skin testing in any of the recipient rats after adoptive transfer. In conclusion, antigen-induced airway bronchoconstriction and eosinophilia were successfully transferred by antigen-specific W3/25+ T cells in Brown Norway rats. These responses were dependent on antigenprimed W3/25+ T cells and appeared to be independent of IgE-mediated mast cell activation. This study provides clear evidence for T cell mediated immune mechanisms in allergic airway responses in this experimental model. (J. Clin. Invest.

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“…Whilst no animal model demonstrates the associated thickening of the reticular basement membrane and remodelling process seen in mild and severe asthma respectively [7,8], the guinea-pig model of acute and late phase reactions to allergen challenge provides a useful experimental means of investigating the inflammatory mediators of importance in allergic reactions [9]. Following their recruitment to tissues, activated eosinophils release preformed toxic cationic granule proteins, such as major basic protein, eosinophil cationic protein and eosinophil peroxidase, which are thought to damage the airway mucosa and lead to the airways hyperresponsiveness of asthma [10][11][12].…”

mentioning

confidence: 99%

Eotaxin protein and gene expression in guinea-pig lungs: constitutive expression and upregulation after allergen challenge

Li¹,

Wang²,

Griffiths-Johnson³

et al. 1997

Eur Respir J

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Eotaxin is an eosinophil-specific chemoattractant originally identified in bronchoalveolar lavage fluid after allergen challenge of sensitized guineapigs. We have determined and quantified for the first time the cellular sources of guinea-pig lung eotaxin and localized gene expression in structural cells of large and small airways and in alveolar macrophages.We used anti-guinea-pig eotaxin monoclonal and polyclonal antibodies and a complementary ribonucleic acid (cRNA) probe to detect eotaxin protein and cytoplasmic messenger ribonucleic acid (mRNA) transcripts by the techniques of immunohistochemistry and in situ hybridization in: 1) naive; 2) ovalbumin-sensitized/ saline-exposed; and 3) ovalbumin-sensitized/ovalbumin-challenged animals (n=5 for each group).Compared with the naive animals, there was a fivefold increase of eotaxin protein and a 25 fold upregulation of eotaxin gene expression in the airway epithelium 3 h after ovalbumin challenge of sensitized animals (p<0.001). The average percentages of alveolar macrophages staining for eotaxin protein and mRNA in the naive animals were approximately 30 and 10% respectively: both increased significantly in the sensitized/ovalbumin-challenged animals to 78 and 57%, respectively (p<0.0001). Compared with the naive animals, the procedure of sensitization and saline exposure significantly increased eotaxin gene expression in both bronchial epithelium and alveolar macrophages (p<0.01): the upregulation at these two sites showed a strong positive association (rcorr=0.95; p<0.0001).The results indicate that there are multiple cellular sources of guinea-pig lungderived eotaxin, including bronchial and bronchiolar epithelial cells, airway smooth muscle, bronchial vascular endothelium, and chondrocytes and alveolar macrophages, and that there are relatively rapid and marked increases of eotaxin protein and gene expression in airway epithelium and alveolar macrophages following allergen challenge.

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T Lymphocytes and Eosinophils in Allergen-induced Late-phase Asthmatic Reactions in the Guinea Pig

Cited by 115 publications

References 7 publications

Time-course of antigen-induced airway inflammation in the guinea-pig and its relationship to airway hyperresponsiveness

Time-course of antigen-induced airway inflammation in the guinea-pig and its relationship to airway hyperresponsiveness

Transfer of allergic airway responses with antigen-primed CD4+ but not CD8+ T cells in brown Norway rats.

Eotaxin protein and gene expression in guinea-pig lungs: constitutive expression and upregulation after allergen challenge

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