YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils
(1998) In Proceedings of the Association of American Physicians 110(4). p.60-351- Abstract
YKL-40, also called human cartilage glycoprotein-39 (HC gp-39), is a member of family 18 glycosyl hydrolases. YKL-40 is secreted by chondrocytes, synovial cells, and macrophages, and recently it has been reported that YKL-40 has a role as an autoantigen in rheumatoid arthritis (RA). The function of YKL-40 is unknown, but the pattern of its expression in normal and disease states suggests that it could function in remodeling or degradation of the extracellular matrix. High levels of YKL-40 are found in synovial fluid from patients with active RA. Neutrophils are abundant in synovial fluid of patients with RA, and the cells are assumed to play a role in joint destruction in that disorder. Therefore, we examined whether neutrophils are a... (More)
YKL-40, also called human cartilage glycoprotein-39 (HC gp-39), is a member of family 18 glycosyl hydrolases. YKL-40 is secreted by chondrocytes, synovial cells, and macrophages, and recently it has been reported that YKL-40 has a role as an autoantigen in rheumatoid arthritis (RA). The function of YKL-40 is unknown, but the pattern of its expression in normal and disease states suggests that it could function in remodeling or degradation of the extracellular matrix. High levels of YKL-40 are found in synovial fluid from patients with active RA. Neutrophils are abundant in synovial fluid of patients with RA, and the cells are assumed to play a role in joint destruction in that disorder. Therefore, we examined whether neutrophils are a source of YKL-40. YKL-40 was found to colocalize and comobilize with lactoferrin (the most abundant protein of specific granules) but not with gelatinase in subcellular fractionation studies on stimulated and unstimulated neutrophils. Double-labeling immunoelectron microscopy confirmed the colocalization of YKL-40 and lactoferrin in specific granules of neutrophils. Immunohistochemistry on bone marrow cells showed that neutrophil precursors begin to synthesize YKL-40 at the myelocyte-metamyelocyte stage, the stage of maturation at which other specific granule proteins are formed. Assuming that YKL-40 has a role as an autoantigen in RA by inducing T cell-mediated autoimmune response, YKL-40 released from neutrophils in the inflamed joint could be essential for this response. In RA and other inflammatory diseases, YKL-40 released from specific granules of neutrophils may be involved in tissue remodeling or degradation.
(Less)
- author
- Volck, B ; Price, P A ; Johansen, J S ; Sørensen, O LU ; Benfield, T L ; Nielsen, H J ; Calafat, J and Borregaard, N
- publishing date
- 1998-08-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adipokines, Cells, Cultured, Chitinase-3-Like Protein 1, Chitinases/biosynthesis, Cytoplasmic Granules/chemistry, Extracellular Matrix Proteins/chemistry, Glycoproteins/biosynthesis, Humans, Immunohistochemistry, Lectins, Neutrophils/enzymology, Subcellular Fractions/metabolism
- in
- Proceedings of the Association of American Physicians
- volume
- 110
- issue
- 4
- pages
- 10 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:0031819084
- pmid:9686683
- ISSN
- 1081-650X
- language
- English
- LU publication?
- no
- id
- 9ae3ccfd-154c-430a-8506-3f37e1e6b1b7
- date added to LUP
- 2020-11-05 13:46:46
- date last changed
- 2024-07-11 01:24:30
@article{9ae3ccfd-154c-430a-8506-3f37e1e6b1b7,
abstract = {{<p>YKL-40, also called human cartilage glycoprotein-39 (HC gp-39), is a member of family 18 glycosyl hydrolases. YKL-40 is secreted by chondrocytes, synovial cells, and macrophages, and recently it has been reported that YKL-40 has a role as an autoantigen in rheumatoid arthritis (RA). The function of YKL-40 is unknown, but the pattern of its expression in normal and disease states suggests that it could function in remodeling or degradation of the extracellular matrix. High levels of YKL-40 are found in synovial fluid from patients with active RA. Neutrophils are abundant in synovial fluid of patients with RA, and the cells are assumed to play a role in joint destruction in that disorder. Therefore, we examined whether neutrophils are a source of YKL-40. YKL-40 was found to colocalize and comobilize with lactoferrin (the most abundant protein of specific granules) but not with gelatinase in subcellular fractionation studies on stimulated and unstimulated neutrophils. Double-labeling immunoelectron microscopy confirmed the colocalization of YKL-40 and lactoferrin in specific granules of neutrophils. Immunohistochemistry on bone marrow cells showed that neutrophil precursors begin to synthesize YKL-40 at the myelocyte-metamyelocyte stage, the stage of maturation at which other specific granule proteins are formed. Assuming that YKL-40 has a role as an autoantigen in RA by inducing T cell-mediated autoimmune response, YKL-40 released from neutrophils in the inflamed joint could be essential for this response. In RA and other inflammatory diseases, YKL-40 released from specific granules of neutrophils may be involved in tissue remodeling or degradation.</p>}},
author = {{Volck, B and Price, P A and Johansen, J S and Sørensen, O and Benfield, T L and Nielsen, H J and Calafat, J and Borregaard, N}},
issn = {{1081-650X}},
keywords = {{Adipokines; Cells, Cultured; Chitinase-3-Like Protein 1; Chitinases/biosynthesis; Cytoplasmic Granules/chemistry; Extracellular Matrix Proteins/chemistry; Glycoproteins/biosynthesis; Humans; Immunohistochemistry; Lectins; Neutrophils/enzymology; Subcellular Fractions/metabolism}},
language = {{eng}},
month = {{08}},
number = {{4}},
pages = {{60--351}},
publisher = {{Wiley-Blackwell}},
series = {{Proceedings of the Association of American Physicians}},
title = {{YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils}},
volume = {{110}},
year = {{1998}},
}