Expression of the Ym2 lectin-binding protein is dependent on interleukin (IL)-4 and IL-13 signal transduction: identification of a novel allergy-associated protein.
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-4Ralpha 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.
Webb
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DC
Division of Biochemistry and Molecular Biology, The John Curtin School of Medical Research, Australian National University, Canberra 2601, Australia.
McKenzie
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Foster
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D000595:Amino Acid Sequence; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology; D006967:Hypersensitivity / Q000378:metabolism*; D018793:Interleukin-13 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D037102:Lectins / Q000032:analysis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D019948:Receptors, Interleukin-4 / Q000502:physiology; D015398:Signal Transduction; D001619:beta-N-Acetylhexosaminidases
D018793:Interleukin-13; D037102:Lectins; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; C429541:Chil3 protein, mouse; D001619:beta-N-Acetylhexosaminidases