title: Acidic mammalian chitinase regulates epithelial cell apoptosis via a chitinolytic-independent mechanism.
abstract: Acidic mammalian chitinase (AMCase) is produced during and plays an important role in the pathogenesis of Th2-mediated diseases and antiparasite responses. However, the effector responses of AMCase in these settings have not been adequately defined and the relationship(s) between its chitinolytic and other biologic properties have not been investigated. In these studies, we demonstrate that AMCase protects airway epithelial cells from Fas ligand- and growth factor withdrawal-induced apoptosis. This cytoprotection was associated with Akt phosphorylation and abrogated when the PI3K/Akt pathway was inhibited. Comparable cytoprotection was also seen in experiments comparing wild-type AMCase and mutant AMCase that lacked chitinolytic activity. Importantly, the apoptosis-inhibiting effect of enzymatically active and inactive AMCase was abrogated by treatment with allosamidin. These studies demonstrate that secreted AMCase feeds back in an autocrine and/or paracrine manner to protect pulmonary epithelial cells from growth factor withdrawal- and Fas ligand-induced apoptosis. They also demonstrate that the cytoprotection is mediated via a PI3K/Akt-dependent and allosamidin-sensitive pathway that is independent of the chitinolytic activity of this chitinase.
authors.affiliation: Department of Internal Medicine, Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Dominik
authors.initials: D
authors.lastname: Hartl
authors.forename: Chuan Hua
authors.initials: CH
authors.lastname: He
authors.forename: Babara
authors.initials: B
authors.lastname: Koller
authors.forename: Carla A
authors.initials: CA
authors.lastname: Da Silva
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Chun Geun
authors.initials: CG
authors.lastname: Lee
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias