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Dr Neil L Misso
Asthma & Allergy Research Institute, School of Medicine and Pharmacology
University of Western Australia
Perth, Western Australia 6009
Email: nmisso@aari.uwa.edu.au
Tel: +61-8-9346-3198
Fax: +61-8-9346-4159
Homepage: http://www.aari.uwa.edu.au

We are investigating the role of the serine proteases, plasma and tissue kallikrein in asthma and chronic obstructive pulmonary disease (COPD). Kallikreins cleave the high- and low-molecular weight kininogens to form the potent inflammatory peptides, bradykinin and lys-bradykinin. Kallikreins are widely distributed in biological fluids, tissues and inflammatory cells and our previous studies identified tissue kallikrein and kinin B1 and B2 receptors on neutrophils. The kallikrein-kinin system of neutrophils has been causally implicated in infection, inflammatory joint disease, transplant rejection, renal glomerular disease, and carcinoma. Kinins formed by the protease activity of kallikreins increase capillary permeability and mediate oedema and pain, stimulate the contraction of bronchial smooth muscle, the release substance P from nerve terminals, and the synthesis of cytokines, prostaglandins, leukotrienes and nitric oxide. Kinins also stimulate proliferation of tumour cells, angiogenesis and diapedesis, thus enhancing metastasis. Our current work is investigating the role of kallikreins, kinins and kinin receptors in dendritic cells and eosinophils. Dendritic cells play a central role in antigen uptake in the airways and in the initiation and amplification of the allergic response, while eosinophils and neutrophils are implicated in the inflammatory processes occurring in asthma and COPD. These studies will provide important information on the role of the kallikrein-kinin system in immune cells and in the modulation of inflammatory processes in lung disease. They may also provide a rational basis for the use of kallikrein inhibitors and kinin receptor antagonists as therapeutic agents for airway inflammation in patients with asthma or COPD.
Professor Khanti Bhoola and Professor Philip Thompson, Asthma & Allergy Research Institute, The University of Western Australia.
Dr. Carlos D. Figueroa, Institute of Histology and Pathology, Austral University, Valdivia, Chile.
Prof. Geoffrey A. Stewart, Microbiology, School of Biomedical and Chemical Sciences, The University of Western Australia, Perth, Australia.
Dr. Johanna Plendl, Institute for Veterinary Anatomy, Free University of Berlin, Berlin, Germany.
Figueroa CD, MacIver AG, Bhoola KD. Identification of a tissue kallikrein in human polymorphonuclear leucocytes. Br J Haematol 1989; 72: 321-328.

Bhoola KD, Figueroa CD, Worthy K. Bioregulation of kinins: kallikreins, kininogens and kininases. Pharmacol Rev 1992; 44: 1-80.

Snyman CJ, Raidoo DM, Bhoola KD. Localization of proteases and peptide receptors by confocal microscopy. Methods Enzymol 1999; 307: 368-394.

Bhoola K, Ramsaroop R, Plendl J, Cassim B, Dlamini Z, Naicker S. Kallikrein and kinin receptor expression in inflammation and cancer. Biol Chem 2001; 382; 77-89.

Stuardo M, Gonzalez CB, Nualart F, Boric M, Corthorn J, Bhoola KD, Figueroa CD. Stimulated human neutrophils form biologically active kinin peptides from high and low molecular weight kininogens. J Leukoc Biol 2004; 75: Epub ahead of print, DOI: 10.1189/jlb.1103546.

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