Allergy and Asthma

Scope

The aim of this program is to establish a physiologically relevant large animal model for allergies and human asthma and to investigate the cellular and molecular pathways of allergic responses.

Fibre-optic bronchoscope used to
investigate allergic asthma in sheep.

Research outline

A sheep model for the study of allergic asthma

Rob Bischof*, Ken Snibson & Els Meeusen*
* Department of Physiology, Monash University

We have established a sheep model of human asthma based on a relevant human allergen, house dust mite (HDM). Sensitised sheep display high HDM-specific IgE serum titres and an elevated bronchoalveolar lavage (BAL) eosinophilia following lung challenge with HDM. Using this model we are able to monitor physiological parameters (airway mechanics) in response to allergen challenge and perform parallel immunological studies. Currently we are investigating the role that different leukocyte populations play in early- and late-phase asthmatic responses. We have also initiated studies to define the role of cellular growth factors, mediators and cytokines on airway remodeling responses in chronic asthmatic lungs.

Compared to small animals, sheep offer a more appropriate model to study the physiological effect of allergic substances on the lung in human asthma, partly due to the anatomical, developmental and electrophysiological similarities between the sheep and human lung. A major advantage of the sheep asthma model is the opportunity to take multiple samples and measurements from one or more lung compartments in one animal. Further, bronchoconstriction can be measured in conscious animals so that there is no confounding effects of anaesthetic agents. The model is therefore ideal for monitoring the kinetics of the asthmatic response and assessing long-term therapeutic procedures.

We anticipate that the results of these studies will lead to more targeted and rational intervention methods and drug design for the control of asthma and other allergic diseases.

Key publications

• Bischof RJ, Snibson K., Shaw R.J. and Meeusen E.N.T. (2003). Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite. Clinical and Experimental Allergy 33: 367-375.
• Dunphy J.L., Barcham G.J., Bischof R.J., Young A.R., Nash A. and Meeusen E.N.T. (2002). Isolation and characterization of a novel eosinophil-specific galectin released into lung fluid in response to allergen-challenge. Journal of Biological Chemistry 277: 14916-14924.
• Bischof R.J. and Meeusen E.N.T. (2002). Cellular kinetics of an allergic-type response in a sheep mammary gland model of inflammation. Clinical and Experimental Allergy 32: 1-8.
• Dunphy J.L., Balic A., Barcham G.J., Horvath A.J., Nash A.D., and Meeusen E.N.T. (2000). Isolation and characterization of a novel inducible mammalian galectin. Journal of Biological Chemistry 275(41):32106-32113.
• Dunphy J., Horvath A., Barcham G., Balic A., Bischof R., Meeusen E.N.T. (2001). Isolation and characterisation of mRNAs encoding the ovine CC chemokines, monocyte chemoattractant protein (MCP) -1a and –2. Veterinary Immunology and Immunopathology 82:153-164.
• Greenhalgh C.J., Jacobs H.J. and Meeusen E.N.T. (1996) An in vivo mammary infusion model for tissue migration of leukocytes during inflammation. Immunology and Cell Biology 74: 497-503.