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Research article2006Peer reviewedOpen access

Serglycin is the major secreted proteoglycan in macrophages and has a role in the regulation of macrophage tumor necrosis factor-alpha secretion in response to lipopolysaccharide

Zernichow L, Abrink M, Hallgren J, Grujic M, Pejler G, Kolset SO

Abstract

It has recently been shown that serglycin is essential for maturation of mast cell secretory granules. However, serglycin is expressed also by other cell types, and in this study we addressed the role of serglycin in macrophages. Adherent cells were prepared from murine peritoneal cell populations and from spleens, and analyzed for proteoglycan synthesis by biosynthetic labeling with [S-35] sulfate. Conditioned media from serglycin(-/-) peritoneal macrophages and adherent spleen cells displayed a 65-80% reduction of S-35-labeled proteoglycans, compared with corresponding material from serglycin(+/+) cells, indicating that serglycin is the dominant secretory proteoglycan in macrophages of these origins. In contrast, the levels of intracellular proteoglycans were similar in serglycin(+/+) and serglycin(-/-) cells, suggesting that serglycin is not stored intracellularly to a major extent in macrophages. This is in contrast to mast cells, in which serglycin is predominantly stored intracellularly. Transmission electron microscopy revealed that the absence of serglycin did not cause any major morphological effects on peritoneal macrophages, in contrast to dramatic defects in intracellular storage vesicles in peritoneal mast cells. Several secretory products were not found to be affected by the lack of serglycin. However, the secretion of tumor necrosis factor-alpha in response to lipopolysaccharide stimulation was markedly higher in serglycin(-/-) cultures than in those of serglycin(+/+). The present report thus demonstrates that serglycin is the major proteoglycan secreted by peritoneal macrophages and suggests that the macrophage serglycin may have a role in regulating secretion of tumor necrosis factor-alpha

Published in

Journal of Biological Chemistry
2006, Volume: 281, number: 37, pages: 26792-26801
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

      SLU Authors

    • Pejler, Gunnar

      • Department of Molecular Biosciences, Swedish University of Agricultural Sciences

        • UKÄ Subject classification

        Veterinary Science
        Animal and Dairy Science

        Publication identifier

        DOI: https://doi.org/10.1074/jbc.M512889200

        Permanent link to this page (URI)

        https://res.slu.se/id/publ/10691