YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils

Proc Assoc Am Physicians. Jul-Aug 1998;110(4):351-60.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines
  • Cells, Cultured
  • Chitinase-3-Like Protein 1
  • Chitinases / biosynthesis*
  • Cytoplasmic Granules / chemistry*
  • Cytoplasmic Granules / ultrastructure
  • Extracellular Matrix Proteins / chemistry*
  • Glycoproteins / biosynthesis*
  • Humans
  • Immunohistochemistry
  • Lectins
  • Neutrophils / enzymology*
  • Neutrophils / ultrastructure
  • Subcellular Fractions / metabolism

Substances

  • Adipokines
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Lectins
  • Chitinases