Expression of the Ym2 Lectin-binding Protein Is Dependent on Interleukin (IL)-4 and IL-13 Signal Transduction

Abstract

Asthma pathophysiology is intimately regulated by CD4؉ Th2 lymphocytes and the cytokines interleukin (IL)-4 and IL-13. However, the mechanisms by which these cytokines promote disease have not been fully elucidated. In order to identify novel molecular mediators of allergy, a comparison was made of the bronchoalveolar lavage, which demonstrated that the Ym2 protein was abundantly up-regulated in the lung during the development of allergy. Low levels of the Ym1 isomer were also detected. Importantly, neither Ym1 nor Ym2 has been characterized previously in the context of allergic pulmonary inflammation. Western immunoblot showed that enhanced expression of these proteins was dependent on CD4؉ T cells and IL-4 or IL-13 signaling via the IL-4R␣ subunit. In addition, intratracheal instillation of IL-13 into naive mice was sufficient to induce expression. Ym1 is homologous to eosinophil chemotactic factor L. However, only weak eosinophil chemotaxis was observed in response to Ym protein in both in vitro and in vivo assays. By contrast, the homology of Ym1 and Ym2 to proteins associated with tissue remodeling, together with the previous findings that Ym1 is homologous to chitinase and binds heparin sulfate and GlcN oligomers (chitobiose, chitotriose, and chitotetraose), strongly suggests these proteins play an important role in airway wall remodeling in the allergic lung.

Global Gene Expression Profiles During Acute Pathogen-Induced Pulmonary Inflammation Reveal Divergent Roles for Th1 and Th2 Responses in Tissue Repair

“…Finally, expression of Ym2, closely related to Ym1, depends upon IL-4R␣ signal transduction (94,95). We show that in the absence of IL-13, Ym1, FIZZ1, and acidic chitinase mRNA are significantly reduced, and their expression correlates with a Th2-polarized phenotype (96,97). The dramatic induction of these genes between days 8 and 14 indicates they may be involved in tissue repair or may simply reflect an increase in the alternatively activated macrophage population.…”

Src homology 2 domain–containing inositol 5-phosphatase 1 deficiency leads to a spontaneous allergic inflammation in the murine lung

“…[23][24][25] Chitinase-like proteins YM-1 and YM-2 had been found in crystal forms in the lungs in mouse models of asthma. 23,24 Crystal particles were readily appreciated in the BAL fluid and in the lungs of SHIP-1 −/− mice (see Fig E6, A, in the Online Repository at www.jacionline.org). RT-PCR confirmed that acidic mammalian chitinase (AMCase), YM-1, and YM-2, but not chitotriosidase, were upregulated in the lungs of SHIP-1 −/− mice (Fig E6, B).…”

Differential expression of chitinases identify subsets of murine airway epithelial cells in allergic inflammation

“…Both Ym1 and Ym2 proteins, related members of the chitinase family, are dramatically upregulated in the presence of Th2 inflammation (43,52,60). To determine whether the staining pattern for AMCase is typical of all members of the chitinase family, we performed in situ hybridization for Ym1 in ovalbumin-challenged and IL-13 transgenic mice ( Figs.…”

“…AMCase has also been suggested to be involved in remodeling of the extracellular matrix (43). Ym1 has been associated with alternatively activated macrophages and has weakly active eosinophil recruiting activity (38,52). Ym1 binds saccharides with a free amine group, including n-glucosamine and their oligosaccharides, as well as heparin, suggesting a role in binding to both extracellular matrix and parasite eggs (8,49).…”