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Science 11 June 2004:
Vol. 304. no. 5677, pp. 1678 - 1682
DOI: 10.1126/science.1095336
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Reports

Acidic Mammalian Chitinase in Asthmatic Th2 Inflammation and IL-13 Pathway Activation

Zhou Zhu,1 Tao Zheng,1 Robert J. Homer,2,3 Yoon-Keun Kim,1 Ning Yuan Chen,1 Lauren Cohn,1 Qutayba Hamid,4 Jack A. Elias1*

Chitin is a surface component of parasites and insects, and chitinases are induced in lower life forms during infections with these agents. Although chitin itself does not exist in humans, chitinases are present in the human genome. We show here that acidic mammalian chitinase (AMCase) is induced via a T helper-2 (Th2)–specific, interleukin-13 (IL-13)–mediated pathway in epithelial cells and macrophages in an aeroallergen asthma model and expressed in exaggerated quantities in human asthma. AMCase neutralization ameliorated Th2 inflammation and airway hyperresponsiveness, in part by inhibiting IL-13 pathway activation and chemokine induction. AMCase may thus be an important mediator of IL-13–induced responses in Th2-dominated disorders such as asthma.

1 Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, Department of Internal Medicine, 300 Cedar Street, TAC S-441, New Haven, CT 06520–8057, USA.
2 Department of Pathology, Yale University School of Medicine, 310 Cedar Street, 108 LH, New Haven, CT 06520–8057, USA.
3 Pathology and Laboratory Medicine Service, VA-CT Health Care System, 950 Campbell Avenue, West Haven, CT 06516, USA.
4 Meakins-Christie Laboratories, 3626 Saint Urbain, McGill University, Montreal, Quebec, H2X 2P2, Canada.

* To whom correspondence should be addressed. E-mail: jack.elias{at}yale.edu

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J. Padilla, E. Daley, A. Chow, K. Robinson, K. Parthasarathi, A. N. J. McKenzie, T. Tschernig, V. P. Kurup, D. D. Donaldson, and G. Grunig (2005)
J. Immunol. 174, 8097-8105
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Ancient Origin of Glycosyl Hydrolase Family 9 Cellulase Genes.
A. Davison and M. Blaxter (2005)
Mol. Biol. Evol. 22, 1273-1284
   Abstract »    Full Text »    PDF »
Identification of a Cooperative Mechanism Involving Interleukin-13 and Eotaxin-2 in Experimental Allergic Lung Inflammation.
S. M. Pope, P. C. Fulkerson, C. Blanchard, H. S. Akei, N. M. Nikolaidis, N. Zimmermann, J. D. Molkentin, and M. E. Rothenberg (2005)
J. Biol. Chem. 280, 13952-13961
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IL-11 Receptor {alpha} in the Pathogenesis of IL-13-Induced Inflammation and Remodeling.
Q. Chen, L. Rabach, P. Noble, T. Zheng, C. G. Lee, R. J. Homer, and J. A. Elias (2005)
J. Immunol. 174, 2305-2313
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Molecular Characterization, Expression, and in Vivo Analysis of LmexCht1: THE CHITINASE OF THE HUMAN PATHOGEN, LEISHMANIA MEXICANA.
M. B. Joshi, M. E. Rogers, A. M. Shakarian, M. Yamage, S. A. Al-Harthi, P. A. Bates, and D. M. Dwyer (2005)
J. Biol. Chem. 280, 3847-3861
   Abstract »    Full Text »    PDF »
Chitin Checking -- Novel Insights into Asthma.
M. Wills-Karp and C. L. Karp (2004)
N. Engl. J. Med. 351, 1455-1457
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