Influence of sensitization and allergen provocation procedures on the development of allergen-induced bronchial hyperreactivity in conscious, unrestrained guinea-pigs

The effects of different sensitization and allergen provocation regimens on the development of allergen-induced bronchial hyperreactivity (BHR) to histamine were investigated in conscious, unrestrained guinea-pigs. Similar early and late phase asthmatic reactions, BHR for inhaled histamine after the early (6 h) as well as after the late reaction (24 h), and airway inflammation were observed after a single allergen provocation in animals sensitized to produce mainly IgG or IgE antibodies, respectively. Repeating the allergen provocation in the IgE-sensitized animals after 7 days, using identical provocation conditions, resulted in a similar development of BHR to histamine inhalation. Repetition of the allergen provocation during 4 subsequent days resulted in a decreased development of BHR after each provocation, despite a significant increase in the allergen provocation dose necessary to obtain similar airway obstruction. The number of inflammatory cells in the bronchoalveolar lavage was not significantly changed after repeated provocation, when compared with a single allergen provocation. Finally, we investigated allergen-induced bronchial hyperreactivity by repetition of the sensitization procedure at day 7 and 14 (booster), followed by repeated allergen provocation twice a week for 5 weeks. Surprisingly, no BHR to histamine could be observed after either provocation, while the number of inflammatory cells in the bronchoalveolar lavage fluid after 5 weeks was enhanced compared with controls. These data indicate that both IgE and IgG sensitized guinea-pigs may develop bronchial hyperreactivity after a single allergen provocation. Repeated allergen exposure of IgE sensitized animals causes a gradual fading of the induced hyperreactivity despite the on-going presence of inflammatory cells in the airways, indicating a mechanism of reduced cellular activation.

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Effects of Roflumilast, Selective PDE4 Inhibitor, on Airway Reactivity in Ovalbumin-Sensitized Guinea Pigs

Acta Medica Martiniana ◽

10.1515/acm-2015-0002 ◽

2015 ◽

Vol 5 (1) ◽

pp. 12-19

Author(s):

Nirmathan Tharmalingam ◽

I. Medvedova ◽

A. Eichlerova ◽

M. Prso ◽

D. Mokra ◽

...

Keyword(s):

Bronchoalveolar Lavage ◽

Guinea Pigs ◽

Bronchoalveolar Lavage Fluid ◽

Inflammatory Cells ◽

Lavage Fluid ◽

Whole Body ◽

Pde4 Inhibitor ◽

Airway Reactivity

Abstract Background: Roflumilast as a phosphodiesterase 4 inhibitor has shown to increase lung functions and decrease the number of exacerbations in chronic obstructive lung disease. In this study, its ability to decrease the airway hyperresponsiveness in a model of eosinophil inflammation was evaluated. Methods: Healthy adult male guinea pigs were divided into groups as follows: the first group was considered as a healthy control group (without sensitization and therapy), animals in the second group were sensitized with ovalbumin, but left without further treatment, and the animals in the third group were sensitized with ovalbumin and treated with roflumilast perorally for 7 consecutive days. In vivo airway reactivity was evaluated using double-chamber whole body plethysmograph and measuring the specific airway resistance after nebulization of histamine aerosol. In vitro experiments were performed with tissue strips of trachea and lungs in organ bath, where their contractile responses to cumulative doses of acetylcholine and histamine were registered. The numbers of inflammatory cells in blood and bronchoalveolar lavage fluid were measured using standard staining. Results: Guinea pigs with roflumilast treatment showed decreased in vivo and in vitro airway reactivity associated with suppressed recruitment of inflammatory cells (especially eosinophils) in blood and bronchoalveolar lavage fluid. Conclusion: Roflumilast has demonstrated the therapeutic potential in the model of ovalbumin induced eosinophil inflammation typically present in patients with bronchial asthma.

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Airway hyperresponsiveness induced by chronic exposure to cigarette smoke in guinea pigs: role of tachykinins

Journal of Applied Physiology ◽

10.1152/jappl.1999.87.5.1621 ◽

1999 ◽

Vol 87 (5) ◽

pp. 1621-1628 ◽

Cited By ~ 36

Author(s):

Zhong-Xin Wu ◽

Lu-Yuan Lee

Keyword(s):

Bronchoalveolar Lavage ◽

Cigarette Smoke ◽

Guinea Pigs ◽

Chronic Exposure ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid ◽

Lung Compliance ◽

Bronchial Hyperreactivity ◽

Mucosal Inflammation ◽

Control Group

This study was carried out to determine whether tachykinins released from lung C-fiber afferents play a part in the bronchial hyperreactivity induced in guinea pigs by chronic exposure to cigarette smoke (CS). Two matching groups of young guinea pigs were exposed to either mainstream CS (CS group) or air (control group) for 20 min twice daily for 14–17 days. There was no difference in the baseline total pulmonary resistance (Rl) between the two groups, but the baseline dynamic lung compliance was reduced (∼19%) in CS animals. The responses of Rl to intravenous injections of ACh, neurokinin (NK) A, and capsaicin were all markedly increased in CS animals; for example, ACh at the same dose of 5.06 μg/kg increased Rl by 207% in the control group and by 697% ( n = 8; P < 0.001) in the CS group. The increased responsiveness was accompanied by significant increases in the numbers of neutrophils, eosinophils, and macrophages in the bronchoalveolar lavage fluid in CS animals. Pretreatment with SR-48968 and CP-99994, antagonists of NK1and NK2 receptors, respectively, did not alter the response of Rlto ACh in control animals, but it abolished the elevated bronchoconstrictive response in the CS animals. Furthermore, the immunoreactivities of substance P and calcitonin gene-related peptide in the bronchoalveolar lavage fluid collected after capsaicin challenge were significantly increased in CS animals. These results show that chronic exposure to CS induced airway mucosal inflammation accompanied by bronchial hyperreactivity in guinea pigs and that the tachykininergic mechanism plays an important role in this augmented responsiveness.

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PAMP is a novel inhibitor of the tachykinin release in the airway of guinea pigs

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1997.272.6.l1066 ◽

1997 ◽

Vol 272 (6) ◽

pp. L1066-L1069

Author(s):

H. Kanazawa ◽

H. Kamoi ◽

T. Kawaguchi ◽

S. Shoji ◽

T. Fujii ◽

...

Keyword(s):

Substance P ◽

Bronchoalveolar Lavage ◽

Guinea Pigs ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid ◽

Neurokinin A ◽

Dependent Manner ◽

C Fiber ◽

Dose Dependent

Proadrenomedullin NH2-terminal 20 peptide (PAMP), a newly identified hypotensive peptide, may play physiological roles in airway and cardiovascular controls. This study was designed to determine the mechanism responsible for the bronchoprotective effects of PAMP on capsaicin-induced bron-choconstriction in anesthetized guinea pigs. PAMP (10(-8)-10(-6) M) significantly inhibited capsaicin-induced bronchoconstriction in a dose-dependent manner. The bronchoprotective effect of PAMP (10(-6) M) was as large as that of isoproterenol (10(-7) M) and lasted > 10 min. The concentration of immunoreactive substance P (SP) in bronchoalveolar lavage fluid after administration of capsaicin (4 x 10(-6) M) was 120 +/- 10 fmol/ml. PAMP significantly inhibited the release of immunoreactive SP in a dose-dependent manner (60 +/- 6 fmol/ml for (10(-6) M PAMP, P < 0.01; 84 +/- 6 fmol/ml for 10(-7) M PAMP, P < 0.01; and 95 +/- 6 fmol/ml for 10(-8) M PAMP, P < 0.05). PAMP (10(-6) M) did not significantly affect exogenous neurokinin A (NKA) or NKA + SP-induced bronchoconstriction, whereas isoproterenol (10(-7) M) significantly inhibited exogenous tachykinin-induced bronchoconstriction. These findings suggest that the bronchoprotective effects of PAMP are mainly due to inhibition of the release of tachykinins at airway C-fiber endings.

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Concentration-Time Models for the Effects of Ozone on Bronchoalveolar Lavage Fluid Protein from Rats and Guinea Pigs

Inhalation Toxicology ◽

10.3109/08958379209145300 ◽

1992 ◽

Vol 4 (1) ◽

pp. 1-16 ◽

Cited By ~ 3

Author(s):

Jerry W. Highfill ◽

Gary E. Hatch ◽

Ralph Slade ◽

Kay M. Crissrnan ◽

Joel Norwood ◽

...

Keyword(s):

Bronchoalveolar Lavage ◽

Guinea Pigs ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid ◽

Concentration Time

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Anti-inflammatory effects of zinc and alterations in zinc transporter mRNA in mouse models of allergic inflammation

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00280.2006 ◽

2007 ◽

Vol 292 (2) ◽

pp. L577-L584 ◽

Cited By ~ 80

Author(s):

Carol Lang ◽

Chiara Murgia ◽

Mary Leong ◽

Lor-Wai Tan ◽

Giuditta Perozzi ◽

...

Keyword(s):

Bronchoalveolar Lavage ◽

Bronchoalveolar Lavage Fluid ◽

Gene Array ◽

Allergic Inflammation ◽

Inflammatory Cells ◽

Lavage Fluid ◽

Mrna Levels ◽

Solute Carrier Family ◽

Zn Uptake ◽

Solute Carrier

There is clinical evidence linking asthma with the trace element, zinc (Zn). Using a mouse model of allergic inflammation, we have previously shown that labile Zn decreases in inflamed airway epithelium (Truong-Tran AQ, Ruffin RE, Foster PS, Koskinen AM, Coyle P, Philcox JC, Rofe AM, Zalewski PD. Am J Respir Cell Mol Biol 27: 286–296, 2002). Moreover, mild nutritional Zn deficiency worsens lung function. Recently, a number of proteins belonging to the Solute Carrier Family 39 (ZIP) and Solute Carrier Family 30 (ZnT) have been identified that bind Zn and regulate Zn homeostasis. Mice were sensitized, and subsequently aerochallenged, with ovalbumin to induce acute and chronic airway inflammation. Mice received 0, 54, or 100 μg of Zn intraperitoneally. Tissues were analyzed for Zn content and histopathology. Inflammatory cells were counted in bronchoalveolar lavage fluid. Cytokine and Zn transporter mRNA levels were determined by cDNA gene array and/or real-time PCR. Zn supplementation decreased bronchoalveolar lavage fluid eosinophils by 40 and 80%, and lymphocytes by 55 and 66%, in the acute and chronic models, respectively. Alterations in Zn transporter expression were observed during acute inflammation, including increases in ZIP1 and ZIP14 and decreases in ZIP4 and ZnT4. Zn supplementation normalized ZIP1 and ZIP14, but it did not affect mRNA levels of cytokines or their receptors. Our results indicate that inflammation-induced alterations in Zn transporter gene expression are directed toward increasing Zn uptake. Increases in Zn uptake may be needed to counteract the local loss of Zn in the airway and to meet an increased demand for Zn-dependent proteins. The reduction of inflammatory cells by Zn in the airways provides support for Zn supplementation trials in human asthmatic individuals.

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