Disease relevance of Chi3l3

• Their expression was also increased in the ears of mice with 2,4-dinitrofluorobenzene-induced contact hypersensitivity, but the increase was greater for Chi3l3 mRNA (51-fold) than Chi3l4 mRNA (32-fold) [1].
• Macrophage expression of Ym1 was highly induced in vivo by an IL-4- and STAT6-dependent mechanism during the evolution of allergic peritonitis, supporting the biological relevance of the IL-4-dependent pathway characterized ex vivo in peritoneal macrophages [2].
• While most resident macrophages in various tissues examined are Ym1-negative, transient expression of Ym1 may be induced in their activated counterparts during inflammation in response to different stimuli in vivo, ranging from various chemical agents to brain injuries [3].
• Upon nematode infection, murine peritoneal macrophages synthesize and secrete large amounts of the Ym1 protein, which is a unique functional marker for alternatively activated macrophages in T(H)2-mediated inflammatory responses [4].
• Three to 5 months after transfer, mice that had received 3 x 10(4) T cells, but not those that received 2 x 10(6), developed fulminant macrophage pneumonia with eosinophilia, Ym1 deposition, and methacholine-induced airway hyperresponsiveness, as well as eosinophilic gastritis; esophagitis and other organ damage occurred in some cases [5].

High impact information on Chi3l3

• Herein, we show that in vivo differentiated SHIP-/- peritoneal (PMPhis) and alveolar (AMPhis) macrophages, unlike their wild-type counterparts, are profoundly M2 skewed (alternatively activated), possessing constitutively high arginase I (ArgI) and Ym1 levels and impaired LPS-induced NO production [6].
• Also, simvastatin was unable to augment Ym1 expression in DCs developed from STAT6-/- or IL-4R alpha-/- mice [7].
• Simvastatin promotes Th2-type responses through the induction of the chitinase family member Ym1 in dendritic cells [7].
• Arginase-1 and Ym1 are markers for murine, but not human, alternatively activated myeloid cells [8].
• Ym1 is a neutrophil granule protein that crystallizes in p47phox-deficient mice [9].

Biological context of Chi3l3

• The crystal structure of a novel mammalian lectin, Ym1, suggests a saccharide binding site [10].
• An ECF-L cDNA clone of 1,506 nucleotides was isolated from a cDNA library, and the nucleotide sequence predicted a mature protein of 397 amino acids [11].
• Molecular characterization of the Ym1 promoter in transfected epithelial and macrophage cell lines revealed the presence of multiple signal transducers and activators of transcription 6 (STAT6) response elements that function in a combinatorial manner to mediate transcriptional responses to IL-4 [2].
• Screening a cDNA library enriched for genes expressed in OCLs identified ECF-L [12].
• The temporal and spatial expression in myeloid precursors and its transient induction in activated macrophages support the notion that Ym1 may be involved in hematopoiesis and inflammation [3].

Anatomical context of Chi3l3

• Treatment of macrophages and mast cells in vitro with interleukin-4 induced expression of Chi3l3 and Chi3l4 mRNA [1].
• ECF-L also attracted T lymphocytes and bone marrow polymorphonuclear leukocytes in vitro, whereas it caused selective extravasation of eosinophils in vivo [11].
• ECF-L mRNA was highly expressed in spleen, bone marrow, lung, and heart [11].
• Ym1 was shown to be a neutrophil granule protein and to have weak beta-N-acetylglucosaminidase activity, indicating that it might contribute to the digestion of glycosaminoglycans [9].
• Ym1, a secretory protein synthesized by activated murine peritoneal macrophages, is a novel mammalian lectin with a binding specificity to GlcN [10].

Associations of Chi3l3 with chemical compounds

• Glycosaminoglycan heparin/heparan sulfate binding ability was also detected in Ym1 [10].
• Although ECF-L contains a consensus CXC sequence near the NH(2) terminus akin to chemokine family proteins, the rest of ECF-L shows poor homology with chemokines [11].
• Transient expression of Ym1, a heparin-binding lectin, during developmental hematopoiesis and inflammation [3].
• X-ray crystallography study revealed that Ym1 has a beta/alpha barrel structure with a carbohydrate-binding cleft similar to that of triose-phosphate isomerases [3].
• Therefore, Ym1 may lack N-acetylglucosamine-binding affinity, and this suggests that a new direction should be taken to unravel the function of Ym1 [4].

Regulatory relationships of Chi3l3

• Eosinophil chemotactic factor-L (ECF-L) enhances osteoclast formation by increasing ICAM-1 expression [13].

Other interactions of Chi3l3

• We mapped the chromosomal location of the Ym1 gene to a central region of mouse chromosome 3 (in the region syntenic to human chromosome 1p13) and that of another murine chitinase-like gene, Brp39, to a central region of mouse chromosome 1 (in the region syntenic to human chromosome 1q31) [14].
• Following re-crystallization at neutral pH, the crystals were identified as the chitinase-like protein Ym1, expressed in organs of the lymphoreticular system, the lung, and distal stomach [9].
• Co-expression of Ym1 with Mac-1 and scavenger receptor pinpoints macrophages as its main producer [15].
• Genomic Southern blot analyses suggest that Ym1 may represent a member of a novel lectin gene family [15].
• The crystal structure of Ym1 consists of two globular domains, a beta/alpha triose-phosphate isomerase barrel domain and a small alpha + beta folding domain [10].

Analytical, diagnostic and therapeutic context of Chi3l3

• We report here the three-dimensional structure of Ym1 at 2.5-A resolution by x-ray crystallography [10].
• By means of surface plasmon resonance analyses, Ym1 has been shown to exhibit binding specificity to saccharides with a free amine group, such as GlcN, GalN, or GlcN polymers, but it failed to bind to other saccharides [15].
• Failure to remove subcutaneous Ym1 crystals injected into knockout mice indicates that a failure of digestion may also contribute to crystallization [9].
• A novel eosinophil chemotactic cytokine (ECF-L) was purified from the culture supernatant of splenocytes of mice by a combination of anion-exchange chromatography, Procion red-agarose affinity chromatography, size exclusion high performance liquid chromatography (HPLC), and reverse phase HPLC [11].
• Time course studies demonstrated that ECF-L acted at the later stages of OCL formation, and chemotactic assays showed that mECF-L increased migration of OCL precursors. mECF-L mRNA was detectable in mononuclear and multinucleated cells by in situ hybridization [12].

References