YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils.
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.
Department of Rheumatology, Hvidovre Hospital, University of Copenhagen, Denmark.
B
B
Volck
P A
PA
Price
J S
JS
Johansen
O
O
Sørensen
T L
TL
Benfield
H J
HJ
Nielsen
J
J
Calafat
N
N
Borregaard
D054392:Adipokines; D002478:Cells, Cultured; D000071451:Chitinase-3-Like Protein 1; D002688:Chitinases / Q000096:biosynthesis*; D003594:Cytoplasmic Granules / Q000737:chemistry* / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D037102:Lectins; D009504:Neutrophils / Q000201:enzymology* / Q000648:ultrastructure; D013347:Subcellular Fractions / Q000378:metabolism
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D037102:Lectins; D002688:Chitinases