Rheumatology, Mast Cell and Protease Biology Group

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The research program is focused on three themes:

1. mast cell biology, including mast cell responses in inflammation and the discovery and molecular characterisation of novel mast cell proteases;
2. cellular recruitment and tissue destructive pathways in synovial inflammation; and
3. cellular responses in autoimmunity.

The overall aim of the research is to characterise the role of the pathophysiological pathways in inflammatory conditions, including rheumatic disease, with a view to development of novel therapies, and the optimisation of health outcomes utilising currrent treatment approaches. Chronic inflammatory diseases that give rise to rheumatic manifestations are studied in the Group, in particular inflammatory polyarthropathies such as rheumatoid arthritis (RA), and systemic autoimmune disorders such as systemic lupus erythematosus (SLE). We have recently established a collaboration with Sanofi-Aventis with the aim of commercializing our discovery of novel proteases.

Researchers

A/Professor Patrick McNeil
Dr John Hunt
Nicole Jackson, PhD Student (submitted)

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Selected Publications

Nicole E. Jackson, Hong-Wei Wang, Nicodemus Tedla, H. Patrick McNeil, Carolyn L. Geczy, Andrew Collins, Michael C. Grimm, Taline Hampartzoumian and John E. Hunt IL-15 induces mast cell migration via a pertussis toxin-sensitive receptor. Eur. J. Immunol. August 2005. 35: 2376-2385.

Wang HW, Tedla N, Hunt JE, Wakefield D, McNeil HP. Mast cell accumulation and cytokine expression in the tight skin mouse model of scleroderma. Exp. Dermatol 2005. 14:295-302

Li M, Liu K, Michalicek J, Angus JA, Hunt JE, Dell’Italia LJ, Feneley MP, Graham RM, Husain A: Involvement of chymase-mediated angiotensin II generation in blood pressure regulation. J Clin Invest. 2004. 114: 112-120.

Hong-Wei Wang, H. Patrick McNeil, Ahsan Husain, Ke Liu, Nicodemus Tedla, Paul S. Thomas, Mark Raftery, Garry C. King, Zhao Yan Cai, and John E. Hunt. Delta Tryptase Is Expressed in Multiple Human Tissues, and a Recombinant Form Has Proteolytic Activity J Immunol 2002 169: 5145-5152.

Hunt JE, Friend DS, Gurish MF, Feyfant E, Sali A, Huang C, Ghildyal N, Stechshulte S, Austen KF and Stevens RL. Mouse Mast Cell Protease 9, a Novel Member of the Chromosome 14 Family of Serine Proteases that is Selectively Expressed in Uterine Mast Cells. J. Biol Chem. 1997, 272: 29158-29166.

Friend DS, Gurish MF, Hunt JE, Austen KF, and Stevens RL. Senescent Jejunal Mast Cells and Eosinophils Preferentially Translocate to the Spleen and Draining Lymph Nodes, Respectively, During the Recovery Phase of Helminth Infection. J. Immunolgy. 2000 165. 344-352.

Huang C, Li L, Krilis SA, Chanasyk K, Tang Y, Li Z, Hunt JE, and Stevens RL. Human Tryptases alpha and beta are functionally distinct, due in part to a single amino acid difference in one of the surface loops that forms the substrate binding cleft. J. Biol Chem. 1999, 274: 19670-19676.

Friend DS, Ghildyal N, Gurish MF, Hunt JE, Hu X, Austen KF, Stevens RL. Recruitment, Reversible Differentiation, and Fate of Mast Cells in the Jejunum of Mice infected with Trichinella spiralis. J. Immunolgy. 1998, 160:5537-5545.

Huang C, Friend DS, Qiu D, Wong GW, Morales G, Hunt JE and Stevens RL. Induction of a Selective and Persistent Extravasation of Neutrophils into the Peritoneal Cavity by the Tryptase Mouse Mast Cell Protease 6. J. Immunol. 1998, 160: 1910-1919.

McNeil HP. Aetiological pathways in osteoarthritis and inflammatory arthritis: rheumatoid arthritis. APLAR J. Rheumatol. 1998.2:139-142.

Gotis-Graham I, Smith M, Parker A, McNeil HP. Synovial mast cell responses during clinical improvement in early rheumatoid arthritis. Annals Rheum. Dis. 1998.57:664-671.

Wang H, Tedla N, Lloyd A, Wakefield D, McNeil HP. Mast cell activation and migration to lymph nodes during induction of an immune response in mice. J.Clin.Invest. 1998.102:1617-1626.

Tedla N, Wang H, McNeil HP, DiGiralamo N, Hampartzoumian T, Wakefield D, Lloyd A. Regulation of T lymphocyte trafficking into lymph nodes during an immune response by the chemokines, MIP-1alpha and MIP-1beta. J.Immunol. 1998;161:5663-5672.

Visvanathan S. McNeil HP. Cellular immunity to b2glycoprotein I in patients with the antiphospholipid syndrome. J.Immunol. 1999;162:6919-6925.

Wong P, McNeil HP, Bertouch JV, Wakefield D, Youssef PP. Monoclonal gammopathy: benign or not? Aust.N.Z.J.Med. 1999.29:278-279.

Field S, Brighton TA, McNeil HP, Chesterman CN. Recent insights into antiphospholipid antibody-mediated thrombosis. Bailliere’s Clinical Haematology 1999.40:407-422.

McNeil HP, Gotis-Graham I. Human mast cell subsets - distinct functions in inflammation ? Inflammation Research. 2000,49:3-7.

Visvanathan S, Geczy CL, Harmer JA, McNeil HP. Monocyte tissue factor induction by activation of b2-glycoprotein-1-specific T lymphocytes is associated with thrombosis and fetal loss in patients with antiphospholipid antibodies. J.Immunol. 2000.165: 2258-2262.

Kumar RK, Temelkovski J, McNeil HP, Hunter N. Airway inflammation in a murine model of chronic asthma: evidence for a local humoral immune response. Clin.Exp.Allergy 2000.30:1486-1492.

Gibson KA, Kumar R, Tedla N, Gotis-Graham I, McNeil HP. Expression of the aEb7 integrin by mast cells in rheumatoid synovium. J.Rheumatol. 2000.27:2754-2760.

Katrib A, Tak PP, Bertouch JV, Cuello C, McNeil HP, Smeets TJ, Kraan MC, Youssef PP. Expression of chemokines and matrix metalloproteinases in early rheumatoid arthritis. Rheumatology 2001;40:988-994.

Lee L, Lawford R, McNeil HP. The efficacy of thalidomide in severe refractory seronegative spondyloarthropathy. Arthritis Rheum. 2001;44:2456-2457.

Lim IGS, Spira PJ, McNeil HP. Headache as the initial presentation of Wegener’s granulomatosis. Annals Rheum.Dis. (in press )